Process for preparing taxoids

Claim 2

A process for preparing a taxoid of the formula I ##STR27## in which R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO in which R 2 represents an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical, and Ar represents an aryl radical, comprising the steps of esterifying a product of the formula VI: ##STR28## in which G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxy-protecting group, with a free acid of the formula VII: ##STR29## in which Ar and R 1 are defined as above, R 3 represents a hydrogen atom or an alkoxy radical containing 1 to 4 carbon atoms or a substituted or unsubstituted aryl radical and R 4 represents a hydrogen atom, to give a compound of the formula II: ##STR30## treating the compound of formula II in acidic medium to give a product of the formula I or a compound of the formula III: ##STR31## wherein G 1 of formula III represents a protecting group that is removed to give a product of formula I.

Claim 3

The process of claim 1, wherein the protecting group is replaced with hydrogen.

Claim 4

The process of claim 1, wherein the esterifying step further comprises using a condensing agent chosen from carbodiimides and reactive carbonates and an activating agent chosen from aminopyridines in an organic solvent chosen from ethers, ketones, esters, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons and aromatic hydrogens at a temperature ranging from -10° to 90° C.

Claim 5

The process of claim 1, wherein the free acid of the esterifying step is in an anhydride form, and wherein the esterifying step is carried out in the presence of an activating agent chosen from aminopyridines in an organic solvent chosen from ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons and aromatic hydrocarbons at a temperature ranging from 0° to 90° C.

Claim 6

The process of claim 1, wherein the free acid of the esterifying step is in a halide form or an anhydride form with an aliphatic or aromatic acid, and wherein the esterifying step is carried out in the presence of a base chosen from tertiary aliphatic amines in an organic solvent chosen from ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from 0° to 80° C.

Claim 7

The process of claim 5, wherein the anhydride form of the free acid is prepared in situ.

Claim 8

The process of claim 1, wherein the acidic medium in the acid treatment step is an inorganic or organic acid in an organic solvent at a temperature ranging from -10° to 60° C.

Claim 9

The process of claim 7, wherein the acid is chosen from at least one of hydrochloric, sulphuric, acetic, methanesulphonic, trifluoromethanesulphonic, and p-toluenesulphonic acids.

Claim 10

The process of claim 7, wherein the solvent is chosen from alcohols, ethers, esters, halogenated aliphatic hydrocarbons, aromatic hydrocarbons, and nitriles.

Claim 11

The process of claim 1, wherein the protecting group G 1 of formula III represents a 2,2,2-trichloroethoxycarbonyl or 2-(2-trichloromethylpropoxy)carbonyl radical and is replaced by a hydrogen atom by treating with zinc or zinc combined with copper in the presence of acetic acid at a temperature ranging from 30° to 60° C. or by treating with an inorganic or organic acid in solution with an aliphatic alcohol containing 1 to 3 carbon atoms or an aliphatic ester in the presence of zinc or zinc combined with copper.

Claim 12

The process of claim 10, wherein the organic acid is selected from hydrochloric and acetic acid.

Claim 13

The process of claim 10, wherein the aliphatic ester is selected from ethyl acetate, isopropyl acetate, and n-butyl acetate.

Claim 14

The process of claim 1, wherein G 1 is an alkoxyacetyl radical and is replaced by a hydrogen by treating in an alkaline medium using ammonia in an aqueous-alcoholic medium at a temperature of about 20° C. or by treating with a zinc halide in methanol at a temperature of about 20° C.

Claim 15

A process for preparing a taxoid of formula I ##STR32## in which R represent a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a radical R 2 --O--CO-- in which R 2 represents an alkyl radical, and Ar represents an aryl radical, comprising the steps of esterifying a product of the formula VI: ##STR33## in which G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxy-protecting group, with a free acid of the formula VII: ##STR34## in which Ar and R 1 are defined as above, R 3 represents a hydrogen atom or an alkoxy radical containing 1 to 4 carbon atoms or a substituted or unsubstituted aryl radical, and R 4 represents a hydrogen atom, to give a compound of the formula II: ##STR35## treating the compound of formula II in acidic medium to give a product of the formula I or a compound of the formula III: ##STR36## wherein G 1 of formula III represents a protecting group that is removed to form a product of formula I.

Claim 16

A process for preparing a taxoid of formula I ##STR32## in which R represent a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a radical R 2 --O--CO-- in which R 2 represents an alkyl radical, and Ar represents an aryl radical, comprising the steps of esterifying a product of the formula VI: ##STR33## in which G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxy-protecting group, with a free acid of the formula VII: ##STR34## in which Ar and R 1 are defined as above, R 3 represents a hydrogen atom or an alkoxy radical containing 1 to 4 carbon atoms or a substituted or unsubstituted aryl radical, and R 4 represents a hydrogen atom, to give a compound of the formula II: ##STR35## treating the compound of formula II in acidic medium to give a product of the formula I or a compound of the formula III: ##STR36## wherein G 1 of formula III represents a protecting group that is removed to form a product of formula I.

Claim 17

The process of claim 14, wherein the protecting group is replaced by a hydrogen atom.

Claim 18

The process of claim 14, wherein the esterifying step further comprises using a condensing agent chosen from carbodiimides and reactive carbonates and an activating agent chosen from aminopyridines in an organic solvent chosen from ethers, ketones, esters, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from -10° to 90° C.

Claim 19

The process of claim 14, wherein the free acid of the esterifying step is in an anhydride form, and wherein the esterifying step is carried out in the presence of an activating agent chosen from aminopyridines in an organic solvent chosen from ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from 0° to 90° C.

Claim 20

The process of claim 14, wherein the free acid of the esterifying step is in a halide form or an anhydride form with an aliphatic or aromatic acid, and wherein the esterifying step is carried out in the presence of a base chosen from tertiary aliphatic amines in an organic solvent chosen from ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from 0° to 80° C.

Claim 21

The process of claim 18, wherein the anhydride form of the free acid is prepared in situ.

Claim 22

The process of claim 14, wherein the acidic medium in the acid treatment step is an inorganic or organic acid in an organic solvent at a temperature ranging from -10° to 60° C.

Claim 23

The process of claim 20, wherein the acid is chosen from at least one of hydrochloric, sulphuric, acetic, methanesulphonic, trifluoromethanesulphonic, and p-toluenesulphonic acids.

Claim 24

The process of claim 20, wherein the solvent is chosen from alcohols, ethers, esters, halogenated aliphatic hydrocarbons, aromatic hydrocarbons, and nitriles.

Claim 25

The process of claim 14, wherein the protecting group G 1 of formula III represents a 2,2,2-trichloroethoxycarbonyl or 2-(2-trichloromethylpropoxy)carbonyl radical and is replaced by a hydrogen atom by treating with zinc or zinc combined with copper in the presence of acetic acid at a temperature ranging from 30° to 60° C. or by treating with an inorganic or organic acid in solution in an aliphatic alcohol containing 1 to 3 carbon atoms or an aliphatic ester in the presence of zinc or zinc combined with copper.

Claim 26

The process of claim 23, wherein the organic acid is selected from hydrochloric and acetic acid.

Claim 27

The process of claim 23, wherein the aliphatic ester is selected from ethyl acetate, isopropyl acetate, and n-butyl acetate.

Claim 28

The process of claim 14, wherein G 1 is an alkoxyacetyl radical and is replaced by a hydrogen atom by treating in an alkaline medium using ammonia in an aqueous-alcoholic medium at a temperature of about 20° C. or by treating with a zinc halide in methanol at a temperature of about 20° C.

Claim 29

A process for preparing a taxoid of the formula I: ##STR37## in which R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical, and Ar represents an aryl radical, comprising the steps of reacting a compound of the formula XXII: ##STR38## with an alkali metal halide or an alkali metal azide or a quaternary ammonium salt or an alkali metal phosphate in an organic solvent to form a compound of the formula VI: ##STR39## in which G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxy protecting group, esterifying the compound of formula VI with a free acid of the formula VII: ##STR40## in which Ar and R 1 are defined as above, R 3 represents a hydrogen atom or an alkoxy radical containing 1 to 4 carbon atoms or a substituted or unsubstituted aryl radical and R 4 represents a hydrogen atom, to give a compound of the formula II: ##STR41## treating the compound of formula II in acidic medium to give a product of the formula I or a compound of the formula III: ##STR42## wherein G 1 represents a protecting group that is removed to give a product of formula I.

Claim 30

A process for preparing a taxoid of the formula I: ##STR37## in which R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical, and Ar represents an aryl radical, comprising the steps of reacting a compound of the formula XXII: ##STR38## with an alkali metal halide or an alkali metal azide or a quaternary ammonium salt or an alkali metal phosphate in an organic solvent to form a compound of the formula VI: ##STR39## in which G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxy protecting group, esterifying the compound of formula VI with a free acid of the formula VII: ##STR40## in which Ar and R 1 are defined as above, R 3 represents a hydrogen atom or an alkoxy radical containing 1 to 4 carbon atoms or a substituted or unsubstituted aryl radical and R 4 represents a hydrogen atom, to give a compound of the formula II: ##STR41## treating the compound of formula II in acidic medium to give a product of the formula I or a compound of the formula III: ##STR42## wherein G 1 represents a protecting group that is removed to give a product of formula I.

Claim 31

The process of claim 27, wherein the protecting group is replaced with hydrogen.

Claim 32

The process of claim 27, wherein the esterifying step further comprises using a condensing agent chosen from carbodiimides and reactive carbonates and an activating agent chosen from aminopyridines in an organic solvent chosen from ethers, ketones, esters, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from -10° to 90° C.

Claim 33

The process of claim 27, wherein the free acid of the esterifying step is in an anhydride form, and wherein the esterifying step is carried out in the presence of an activating agent chosen from aminopyridines in an organic solvent chosen from ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from 0° to 90° C.

Claim 34

The process of claim 27, wherein the free acid of the esterifying step is in a halide form or an anhydride form with an aliphatic or aromatic acid, and wherein the esterifying step is carried out in the presence of a base chosen from tertiary aliphatic amines in an organic solvent chosen from ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from 0° to 80° C.

Claim 35

The process of claim 31, wherein the anhydride form of the free acid is prepared in situ.

Claim 36

The process of claim 27, wherein the acid medium of the acid treatment step is an inorganic or organic acid in an organic solvent at a temperature ranging from -10° to 60° C.

Claim 37

The process of claim 33, wherein the acid is chosen from at least one of hydrochloric, sulphuric, acetic, methanesulphonic, trifluoromethanesulphonic, and p-toluenesulponic acids.

Claim 38

The process of claim 33, wherein the solvent is chosen from alcohols, ethers, esters, halogenated aliphatic hydrocarbons, aromatic hydrocarbons, and nitriles.

Claim 39

The process of claim 27, wherein the protecting group G 1 of formula III represents a 2,2,2-trichloroethoxycarbonyl or 2-(2-trichloromethylpropoxy)carbonyl radical and is replaced by a hydrogen atom by treating with zinc or zinc combined with copper in the presence of acetic acid at a temperature ranging from 30° to 60° C. or by treating with an inorganic or organic acid in solution in an aliphatic alcohol containing 1 to 3 carbon atoms or an aliphatic ester in the presence of zinc or zinc combined with copper.

Claim 40

The process of claim 36, wherein the organic acid is selected from hydrochloric and acetic acid.

Claim 41

The process of claim 36, wherein the aliphatic ester is selected from ethyl acetate, isopropyl acetate, and n-butyl acetate.

Claim 42

The process of claim 27, wherein G 1 is an alkoxyacetyl radical and is replaced by a hydrogen by treating in an alkaline medium using ammonia in an aqueous-alcoholic medium at a temperature of about 20° C. or by treating with a zinc halide in methanol at a temperature of about 20° C.

Claim 43

A process for preparing a taxoid of the formula I: ##STR43## in which R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents an alkyl, alkenyl, alkynyl, cycloalky, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical, and Ar represents an aryl radical, comprising the steps of reacting a compound of the formula XXII: ##STR44## with an alkali metal halide or an alkali metal azide or a quaternary ammonium salt or an alkali metal phosphate in an organic solvent to form a compound of the formula VI: ##STR45## in which G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxyprotecting group, esterifying a compound of the formula VI with a free acid of the formula VII: ##STR46## in which Ar and R 1 are defined as above, R 3 and R 4 , which are identical or different, represent an alkyl radical containing 1 to 4 carbon atoms or an aralkyl radica whose alkyl portion contains 1 to 4 carbon atoms or an aryl radical, or R 3 represents a trihalomethyl radical or a phenyl radical substituted by a trihalomethyl radical and R 4 represents a hydrogen atom, or R 3 and R 4 form, together with the carbon atom to which they are attached, a 4- to 7-membered ring, to give, after treating in acidic medium, a compound of the formula IV: ##STR47## and acylating the compound of formula IV with benzoyl chloride or a reactive derivative of the formula: R.sub.2 --O--CO--X in which X represents a halogen atom or a residue --O--R 2 or --O--CO--O--R 2 and R 2 is as defined above, to give a product of formula I or a compound of formula III ##STR48## wherein G 1 represents a protecting group that is removed to give a product of formula I.

Claim 44

A process for preparing a taxoid of the formula I: ##STR43## in which R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents an alkyl, alkenyl, alkynyl, cycloalky, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical, and Ar represents an aryl radical, comprising the steps of reacting a compound of the formula XXII: ##STR44## with an alkali metal halide or an alkali metal azide or a quaternary ammonium salt or an alkali metal phosphate in an organic solvent to form a compound of the formula VI: ##STR45## in which G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxyprotecting group, esterifying a compound of the formula VI with a free acid of the formula VII: ##STR46## in which Ar and R 1 are defined as above, R 3 and R 4 , which are identical or different, represent an alkyl radical containing 1 to 4 carbon atoms or an aralkyl radica whose alkyl portion contains 1 to 4 carbon atoms or an aryl radical, or R 3 represents a trihalomethyl radical or a phenyl radical substituted by a trihalomethyl radical and R 4 represents a hydrogen atom, or R 3 and R 4 form, together with the carbon atom to which they are attached, a 4- to 7-membered ring, to give, after treating in acidic medium, a compound of the formula IV: ##STR47## and acylating the compound of formula IV with benzoyl chloride or a reactive derivative of the formula: R.sub.2 --O--CO--X in which X represents a halogen atom or a residue --O--R 2 or --O--CO--O--R 2 and R 2 is as defined above, to give a product of formula I or a compound of formula III ##STR48## wherein G 1 represents a protecting group that is removed to give a product of formula I.

Claim 45

The process of claim 40, wherein the protecting group is replaced by a hydrogen atom.

Claim 46

The process of claim 40, wherein the esterifying step further comprises using a condensing agent chosen from carbodiimides and reactive carbonates and an activating agent chosen from aminopyridines in an organic solvent chosen from ethers, ketones, esters, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from -10° to 90° C.

Claim 47

The process of claim 39, wherein the free acid of the esterifying step is in an anhydride form, and wherein the esterifying step is carried out in the presence of an activating agent chosen from aminopyridines in an organic solvent chosen from ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from 0° to 90° C.

Claim 48

The process of claim 40, wherein the free acid of the esterifying step is in a halide form or an anhydride form with an aliphatic or aromatic acid, and wherein the esterifying step is carried out in the presence of a base chosen from tertiary aliphatic amines in an organic solvent chosen from ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from 0° to 80° C.

Claim 49

The process of claim 40, wherein the acid medium of the acid treatment step is an inorganic or organic acid in an organic solvent at a temperature ranging from 0° to 50° C.

Claim 50

The process of claim 45, wherein the acid is chosen from hydrochloric, sulphuric, and formic acids.

Claim 51

The process of claim 45, wherein the solvent is chosen from alcohols containing 1 to 3 carbon atoms.

Claim 52

The process of claim 40, wherein the acylating step further comprises using an inert organic solvent in the presence of an inorganic or organic base.

Claim 53

The process of claim 48, wherein the inert organic solvent is chosen from esters, and halogenated aliphatic hydrocarbons.

Claim 54

The process of claim 40, wherein the protecting group G 1 of formula III represents a 2,2,2-trichloroethoxycarbonyl or 2-(2-trichloromethyl-propoxy)carbonyl radical and is replaced by a hydrogen atom by treating with zinc or zinc combined with copper in the presence of acetic acid at a temperature ranging from 30° to 60° C. or by treating with an inorganic or organic acid in solution in an aliphatic alcohol containing 1 to 3 carbon atoms or an aliphatic ester in the presence of zinc or zinc combined with copper.

Claim 55

The process of claim 43, wherein the anhydride form of the free acid is prepared in situ.

Claim 56

The process of claim 50, wherein the aliphatic ester is selected from ethyl acetate, isopropyl acetate, and n-butyl acetate.

Claim 57

The process of claim 40, wherein G 1 is an alkoxyacetyl radical and is replaced by a hydrogen by treating in an alkaline medium using ammonia in an aqueous-alcoholic medium at a temperature of about 20° C. or by treating with a zinc halide in methanol at a temperature of about 20° C.

Claim 58

A process for preparing a taxoid of the formula I: ##STR49## in which R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical, and Ar represents an aryl radical comprising the steps of reacting a compound of the formula XXII: ##STR50## in which G 1 represents a hydrogen atom or an acetyl or alkoxyacetyl radical or a hydroxy-protecting group, with an alkali metal halide or an alkali metal azide or a quaternary ammonium salt or an alkali metal phosphate in an organic solvent to form a compound of the formula VI: ##STR51## esterifying the compound of the formula VI with an acid of the formula XXVI: ##STR52## in which Ar and R 1 are defined as above, G 3 represents a hydroxy-protecting group, or an activated derivative of the acid of formula XXVI, to give a compound of the formula XXVII: ##STR53## replacing the protecting group G 3 with hydrogen to give a product of formula I and when G 1 represents a protecting group, replacing said G 1 protecting group to give a product of formula I.

Claim 59

A process for preparing a taxoid of the formula I: ##STR49## in which R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical, and Ar represents an aryl radical comprising the steps of reacting a compound of the formula XXII: ##STR50## in which G 1 represents a hydrogen atom or an acetyl or alkoxyacetyl radical or a hydroxy-protecting group, with an alkali metal halide or an alkali metal azide or a quaternary ammonium salt or an alkali metal phosphate in an organic solvent to form a compound of the formula VI: ##STR51## esterifying the compound of the formula VI with an acid of the formula XXVI: ##STR52## in which Ar and R 1 are defined as above, G 3 represents a hydroxy-protecting group, or an activated derivative of the acid of formula XXVI, to give a compound of the formula XXVII: ##STR53## replacing the protecting group G 3 with hydrogen to give a product of formula I and when G 1 represents a protecting group, replacing said G 1 protecting group to give a product of formula I.

Claim 60

The process of claim 54, wherein the G 1 protecting group is replaced by a hydrogen atom.

Claim 61

The process of claim 54, wherein the esterifying step further comprises using a condensing agent chosen from carbodiimides and reactive carbonates and an activating agent chosen from aminopyridines in an organic solvent chosen from ethers, ketones, esters, nitriles aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from -10° to 90° C.

Claim 62

The process of claim 54, wherein the acid of the esterifying step is in an anhydride form, and wherein the esterifying step is carried out in the presence of an activating agent chosen from aminopyridines in an organic solvent chosen from ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from 0° to 90° C.

Claim 63

The process of claim 54, wherein the acid of the esterifying step is in a halide form or an anhydride form with an aliphatic or aromatic acid, and wherein the esterifying step is carried out in the presence of a base chosen from tertiary aliphatic amines in an organic solvent chosen from ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, and aromatic hydrocarbons at a temperature ranging from 0° to 80° C.

Claim 64

The process of claim 58, wherein the anhydride form of the acid is prepared in situ.

Claim 65

The process of claim 54, wherein the protecting groups G 1 and G 3 represent a 2,2,2-trichloroethoxycarbonyl or 2-(2-trichloro-methylpropoxy)carbonyl radical and are replaced with hydrogen atoms by treating with zinc or zinc combined with copper in the presence of acetic acid at a temperature of between 30° and 60° C. or by treating with an inorganic or organic acid in solution in an aliphatic alcohol containing 1 to 3 carbon atoms or an aliphatic ester in the presence of zinc or zinc combined with copper.

Claim 66

The process of claim 54, wherein the protecting group G 3 represents a silylated radical or acetal residue and is replaced with hydrogen by treating in acidic medium in solution in an aliphatic alcohol containing 1 to 3 carbon atoms or aqueous hydrofluoric acid at a temperature ranging from 0° to 40° C., followed by the replacement of the protecting group G 1 with hydrogen by treating with zinc or zinc combined with copper in the presence of acetic acid at a temperature ranging from 30° to 60° C. or by treating with an inorganic or organic acid in solution in an aliphatic alcohol containing 1 to 3 carbon atoms or an aliphatic ester in the presence of zinc or zinc combined with copper.

Claim 67

The process of claim 53, wherein G 1 is an alkoxyacetyl radical and is replaced by a hydrogen by treating in an alkaline medium using ammonia in an aqueous-alcoholic medium at a temperature of about 20° C. or by treating with a zinc halide in methanol at a temperature of about 20° C.

Claim 68

The process of claim 60, wherein the organic acid is hydrochloric or acetic acid.

Claim 69

The process of claim 60, wherein the aliphatic ester represents ethyl acetate, isopropyl acetate, or n-butyl acetate.

Claim 70

The process of claim 54, wherein G 3 represents a radical --CH 2 --Ph and is replaced by a hydrogen atom using hydrogenolysis after replacing the protecting group G 1 .