Cyanohydrin process

Claim 2

A steroid selected from the group consisting of a 21-haloenimide of the formula ##STR55## and a 21-halo-Δ 20 -enamide of the formula ##STR56## and C 3 protected forms thereof where R 6 is a hydrogen or fluorine atom or methyl group; R 9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring (a) Δ 9 (11) when R 9 is nothing and (b) 9β,11-epoxide when R 9 is an oxygen atom; R 11 is a hydrogen or oxygen atom, two hydrogen atoms, or α- or β-hydroxyl group which makes the C-ring (a) Δ 9 (11) when R 11 is a hydrogen atom, (b) 9β,11β-epoxide when R 11 is an oxygen atom and between C 11 and R 11 is a single bond, and (c) a ketone when R 11 is an oxygen atom and between C 11 and R 11 is a double bond; R 16 is a hydrogen atom or methyl group; R 20 is --OC--R 20 ' or --R 20 "; R 20 ' is alkyl of 1 thru 5 carbon atoms, phenyl, phenyl substituted 0 thru 2 chlorine atoms, methyl or nitro groups; R 20 " is --Si(CH 3 ) 3 or --SI(CH 3 ) 2 C(CH 3 ) 3 ; X refers to a hydrogen atom or nothing; Z is selected from the group consisting of a TMS, THP, methoxymethyl, t-butyl-dimethyl silyl and EEE group; is a single or double bond; ˜ indicates that the attached atom or group can be in either the a or β configurations; and Hal is a chlorine, bromine, iodine, atom.

Claim 3

A steroid according to claim 1 where the Δ 4 -3-keto steroid (A) is protected as the ##STR57## where the Δ 1 ,4 -3-keto steroid (B) is protected as the ##STR58## and where the 3β-hydroxy-Δ 5 steroid (C) is protected as the ##STR59## where R 3 is alkyl of 1 thru 5 carbon atoms with the proviso that for the ketal (Ab) and the enamine (Ac), the R 3 groups can be connected and when connected may be connected by an oxygen or nitrogen atom; M is a lithium, sodium, potassium, magnesium or calcium atom; and W is a TMS, THP, or ethoxy ethyl group.

Claim 4

A steroid according to claim 1 where R 9 is nothing, R 11 is a hydrogen atom and the C-ring contains a Δ 9 ,11 double bond.

Claim 5

A steroid according to claim 1 where Z is selected from the group consisting of EEE, THP, TMS, and MEM.

Claim 6

A steroid according to claim 1 where R 20 is selected from the group consisting of acetyl, propionyl, benzoyl, formyl, trichloroacetyl and trifluoroacetyl.

Claim 7

A steroid according to claim 1 where Hal is a bromine atom.

Claim 8

A process for the preparation of a C 3 protected form of an oxazoline of the formula ##STR60## which comprises contacting a steroid selected from the group consisting of a C 3 protected form of an enimide of the formula ##STR61## or a C 3 protected form of a Δ 20 -enamide of the formula ##STR62## with an acid in an organic solvent or mixtures thereof where R 6 is a hydrogen or fluorine atom or methyl group; R 9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring (a) Δ 9 (11) when R 9 is nothing and (b) 9β,11-epoxide when R 9 is an oxygen atom; R 11 is a hydrogen or oxygen atom, two hydrogen atoms, or α- or β-hydroxyl group which makes the C-ring (a) Δ 9 (11) when R 11 is a hydrogen atom, (b) 9β,11β-epoxide when R 11 is an oxygen atom and between C 11 and R 11 is a single bond, and (c) a ketone when R 11 is an oxygen atom and between C 11 and R 11 is a double bond; R 16 is a hydrogen atom or methyl group; R 17 is a hydrogen atom alkyl of 1 thru 5 carbon atoms, phenyl substituted with zero thru 2 chlorine atoms, trichloromethyl, or trifluoromethyl groups; R 20 is --OC--R 20 ' or --R 20 "; R 20 ' is alkyl of 1 thru 5 carbon atoms, phenyl, phenyl substituted 0 thru 2 chlorine atoms, methyl or nitro groups; R 20 " is --Si(CH 3 ) 3 or --SI(CH 3 ) 2 C(CH 3 ) 3 ; X refers to a hydrogen atom or nothing; Z is selected from the group consisting of a TMS, THP, methoxymethyl, t-butyl-dimethyl silyl and EEE group; is a single or double bond; and ˜ indicates that the attached atom or group can be in either the a or β configurations.

Claim 9

A process for the preparation of a C 3 protected form of an oxazoline of the formula ##STR60## which comprises contacting a steroid selected from the group consisting of a C 3 protected form of an enimide of the formula ##STR61## or a C 3 protected form of a Δ 20 -enamide of the formula ##STR62## with an acid in an organic solvent or mixtures thereof where R 6 is a hydrogen or fluorine atom or methyl group; R 9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring (a) Δ 9 (11) when R 9 is nothing and (b) 9β,11-epoxide when R 9 is an oxygen atom; R 11 is a hydrogen or oxygen atom, two hydrogen atoms, or α- or β-hydroxyl group which makes the C-ring (a) Δ 9 (11) when R 11 is a hydrogen atom, (b) 9β,11β-epoxide when R 11 is an oxygen atom and between C 11 and R 11 is a single bond, and (c) a ketone when R 11 is an oxygen atom and between C 11 and R 11 is a double bond; R 16 is a hydrogen atom or methyl group; R 17 is a hydrogen atom alkyl of 1 thru 5 carbon atoms, phenyl substituted with zero thru 2 chlorine atoms, trichloromethyl, or trifluoromethyl groups; R 20 is --OC--R 20 ' or --R 20 "; R 20 ' is alkyl of 1 thru 5 carbon atoms, phenyl, phenyl substituted 0 thru 2 chlorine atoms, methyl or nitro groups; R 20 " is --Si(CH 3 ) 3 or --SI(CH 3 ) 2 C(CH 3 ) 3 ; X refers to a hydrogen atom or nothing; Z is selected from the group consisting of a TMS, THP, methoxymethyl, t-butyl-dimethyl silyl and EEE group; is a single or double bond; and ˜ indicates that the attached atom or group can be in either the a or β configurations.

Claim 10

A process according to claim 7 where the Δ 4 -3-keto steroid (A) is protected as the ##STR63## where the Δ 1 ,4 -3-keto steroid (B) is protected as the ##STR64## and where the 3β-hydroxy-Δ 5 steroid (C) is protected as the ##STR65## where R 3 is alkyl of 1 thru 5 carbon atoms with the proviso that for the ketal (Ab) and the enamine (Ac), the R 3 groups can be connected and when connected may be connected by an oxygen or nitrogen atom; M is a lithium, sodium, potassium, magnesium or calcium atom; and W is a TMS, THP, or ethoxy ethyl group.

Claim 11

A process according to claim 7 where the acid is selected from the group consisting of mineral inorganic acids, organic acids and Lewis acids.

Claim 12

A process according to claim 9 where the acid is selected from the group consisting of p-TSA, acetic, sulfuric, hydrochloric, phosphoric, formic, and benzoic.

Claim 13

A process for the preparation of a steroid selected from the group consisting of a C 3 protected form of a 21-halo enimide of the formula ##STR66## and a C 3 protected form of a 21-halo-Δ 20 -enamide of the formula ##STR67## which comprises contacting a C 3 protected form of a Δ 20 -enamide of the formula ##STR68## with a halogenating agent where R 6 is a hydrogen or fluorine atom or methyl group; R 9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring (a) Δ 9 (11) when R 9 is nothing and (b) 9β,11-epoxide when R 9 is an oxygen atom; R 11 is a hydrogen or oxygen atom, two hydrogen atoms, or α- or β-hydroxyl group which makes the C-ring (a) Δ 9 (11) when R 11 is a hydrogen atom, (b) 9β,11β-epoxide when R 11 is an oxygen atom and between C 11 and R 11 is a single bond, and (c) a ketone when R 11 is an oxygen atom and between C 11 and R 11 is a double bond; R 16 is a hydrogen atom or methyl group; R 20 is --OC--R 20 ' or --R 20 "; R 20 ' is alkyl of 1 thru 5 carbon atoms, phenyl, phenyl substituted 0 thru 2 chlorine atoms, methyl or nitro groups; R 20 " is --Si(CH 3 ) 3 or --SI(CH 3 ) 2 C(CH 3 ) 3 ; Z is selected from the group consisting of a TMS, THP, methoxymethyl, t-butyl-dimethyl silyl and EEE group; X refers to a hydrogen atom or nothing; is a single or double bond; ˜ indicates that the attached atom or group can be in either the a or β configurations; Hal is a chlorine, bromine, iodine, atom.

Claim 14

A process for the preparation of a steroid selected from the group consisting of a C 3 protected form of a 21-halo enimide of the formula ##STR66## and a C 3 protected form of a 21-halo-Δ 20 -enamide of the formula ##STR67## which comprises contacting a C 3 protected form of a Δ 20 -enamide of the formula ##STR68## with a halogenating agent where R 6 is a hydrogen or fluorine atom or methyl group; R 9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring (a) Δ 9 (11) when R 9 is nothing and (b) 9β,11-epoxide when R 9 is an oxygen atom; R 11 is a hydrogen or oxygen atom, two hydrogen atoms, or α- or β-hydroxyl group which makes the C-ring (a) Δ 9 (11) when R 11 is a hydrogen atom, (b) 9β,11β-epoxide when R 11 is an oxygen atom and between C 11 and R 11 is a single bond, and (c) a ketone when R 11 is an oxygen atom and between C 11 and R 11 is a double bond; R 16 is a hydrogen atom or methyl group; R 20 is --OC--R 20 ' or --R 20 "; R 20 ' is alkyl of 1 thru 5 carbon atoms, phenyl, phenyl substituted 0 thru 2 chlorine atoms, methyl or nitro groups; R 20 " is --Si(CH 3 ) 3 or --SI(CH 3 ) 2 C(CH 3 ) 3 ; Z is selected from the group consisting of a TMS, THP, methoxymethyl, t-butyl-dimethyl silyl and EEE group; X refers to a hydrogen atom or nothing; is a single or double bond; ˜ indicates that the attached atom or group can be in either the a or β configurations; Hal is a chlorine, bromine, iodine, atom.

Claim 15

A process according to claim 11 where the Δ 4 -3-keto steroid (A) is protected as the ##STR69## where the Δ 1 ,4 -3-keto steroid (B) is protected as the ##STR70## and where the 3β-hydroxy-Δ 5 steroid (C) is protected as the ##STR71## where R 3 is alkyl of 1 thru 5 carbon atoms with the proviso that for the ketal (Ab) and the enamine (Ac), the R 3 groups can be connected and when connected may be connected by an oxygen or nitrogen atom; M is a lithium, sodium, potassium, magnesium or calcium atom; and W is a TMS, THP, or ethoxy ethyl group.

Claim 16

A process according to claim 11 where the halogenating agent is selected from the group consisting of bromine, NBS, NCS, dibromatin, pyridine hydrobromide.

Claim 17

A process for preparing a C 3 protected form of a 17α-hydroxy steroid of the formula ##STR72## which comprises (1) contacting a steroid selected from the group consisting of a C 3 protected form of a 21-halo enimide of the formula ##STR73## or a C 3 protected 21-halo-Δ 20 -enamide of the formula ##STR74## with an (aqueous) acid where R 6 is a hydrogen or fluorine atom or methyl group; R 9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring (a) Δ 9 (11) when R 9 is nothing and (b) 9β,11-epoxide when R 9 is an oxygen atom; R 11 is a hydrogen or oxygen atom, two hydrogen atoms, or α- or β-hydroxyl group which makes the C-ring (a) Δ 9 (11) when R 11 is a hydrogen atom, (b) 9β,11β-epoxide when R 11 is an oxygen atom and between C 11 and R 11 is a single bond, and (c) a ketone when R 11 is an oxygen atom and between C 11 and R 11 is a double bond; R 16 is a hydrogen atom or methyl group; R 20 is --OC--R 20 ' or --R 20 "; R 20 ' is alkyl of 1 thru 5 carbon atoms, phenyl, phenyl substituted 0 thru 2 chlorine atoms, methyl or nitro groups; R 20 " is --Si(CH 3 ) 3 or --SI(CH 3 ) 2 C(CH 3 ) 3 ; X refers to a hydrogen atom or nothing; Z is selected from the group consisting of a TMS, THP, methoxymethyl, t-butyl-dimethyl silyl and EEE group; Hal is a chlorine, bromine, iodine, atom; is a single or double bond; and ˜ indicates that the attached atom or group can be in either the a or β configurations.

Claim 18

A process for preparing a C 3 protected form of a 17α-hydroxy steroid of the formula ##STR72## which comprises (1) contacting a steroid selected from the group consisting of a C 3 protected form of a 21-halo enimide of the formula ##STR73## or a C 3 protected 21-halo-Δ 20 -enamide of the formula ##STR74## with an (aqueous) acid where R 6 is a hydrogen or fluorine atom or methyl group; R 9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring (a) Δ 9 (11) when R 9 is nothing and (b) 9β,11-epoxide when R 9 is an oxygen atom; R 11 is a hydrogen or oxygen atom, two hydrogen atoms, or α- or β-hydroxyl group which makes the C-ring (a) Δ 9 (11) when R 11 is a hydrogen atom, (b) 9β,11β-epoxide when R 11 is an oxygen atom and between C 11 and R 11 is a single bond, and (c) a ketone when R 11 is an oxygen atom and between C 11 and R 11 is a double bond; R 16 is a hydrogen atom or methyl group; R 20 is --OC--R 20 ' or --R 20 "; R 20 ' is alkyl of 1 thru 5 carbon atoms, phenyl, phenyl substituted 0 thru 2 chlorine atoms, methyl or nitro groups; R 20 " is --Si(CH 3 ) 3 or --SI(CH 3 ) 2 C(CH 3 ) 3 ; X refers to a hydrogen atom or nothing; Z is selected from the group consisting of a TMS, THP, methoxymethyl, t-butyl-dimethyl silyl and EEE group; Hal is a chlorine, bromine, iodine, atom; is a single or double bond; and ˜ indicates that the attached atom or group can be in either the a or β configurations.

Claim 19

A process according to claim 14 where the Δ 4 -3-keto steroid (A) is protected as the ##STR75## where the Δ 1 ,4 -3-keto steroid (B) is protected as the ##STR76## and where the 3β-hydroxy-Δ 5 steroid (C) is protected as the ##STR77## where R 3 is alkyl of 1 thru 5 carbon atoms with the proviso that for the ketal (Ab) and the enamine (Ac), the R 3 groups can be connected and when connected may be connected by an oxygen or nitrogen atom; M is a lithium, sodium, potassium, magnesium or calcium atom; and W is a TMS, THP, or ethoxy ethyl group.

Claim 20

A process according to claim 14 where the acid is an inorganic mineral acid.

Claim 21

A process according to claim 16 where the acid is sulfuric acid and the solvent is THF.

Claim 22

A Δ 20 -enamide acylate of the formula ##STR78## and C 3 protected forms thereof where R 6 is a hydrogen or fluorine atom or methyl group; R 9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring (a) Δ 9 (11) when R 9 is nothing and (b) 9β,11-epoxide when R 9 is an oxygen atom; R 11 is a hydrogen or oxygen atom, two hydrogen atoms, or α- or β-hydroxyl group which makes the C-ring (a) Δ 9 (11) when R 11 is a hydrogen atom, (b) 9β,11β-epoxide when R 11 is an oxygen atom and between C 11 and R 11 is a single bond, and (c) a ketone when R 11 is an oxygen atom and between C 11 and R 11 is a double bond; R 16 is a hydrogen atom or methyl group; R 17 is a hydrogen atom alkyl of 1 thru 5 carbon atoms, phenyl substituted with zero thru 2 chlorine atoms, trichloromethyl, or trifluoromethyl groups; R 20 is --OC--R 20 ' or --R 20 "; R 20 ' is alkyl of 1 thru 5 carbon atoms, phenyl, phenyl substituted 0 thru 2 chlorine atoms, methyl or nitro groups; R 20 " is --Si(CH 3 ) 3 or --SI(CH 3 ) 2 C(CH 3 ) 3 ; is a single or double bond; and ˜ indicates that the attached atom or group can be in either the a or β configurations.

Claim 23

A Δ 20 -enamide acylate of the formula ##STR78## and C 3 protected forms thereof where R 6 is a hydrogen or fluorine atom or methyl group; R 9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring (a) Δ 9 (11) when R 9 is nothing and (b) 9β,11-epoxide when R 9 is an oxygen atom; R 11 is a hydrogen or oxygen atom, two hydrogen atoms, or α- or β-hydroxyl group which makes the C-ring (a) Δ 9 (11) when R 11 is a hydrogen atom, (b) 9β,11β-epoxide when R 11 is an oxygen atom and between C 11 and R 11 is a single bond, and (c) a ketone when R 11 is an oxygen atom and between C 11 and R 11 is a double bond; R 16 is a hydrogen atom or methyl group; R 17 is a hydrogen atom alkyl of 1 thru 5 carbon atoms, phenyl substituted with zero thru 2 chlorine atoms, trichloromethyl, or trifluoromethyl groups; R 20 is --OC--R 20 ' or --R 20 "; R 20 ' is alkyl of 1 thru 5 carbon atoms, phenyl, phenyl substituted 0 thru 2 chlorine atoms, methyl or nitro groups; R 20 " is --Si(CH 3 ) 3 or --SI(CH 3 ) 2 C(CH 3 ) 3 ; is a single or double bond; and ˜ indicates that the attached atom or group can be in either the a or β configurations.

Claim 24

A 17β-cyano-17α-hydroxy steroid of the formula ##STR79## and C 3 protected forms thereof where R 6 is a hydrogen or fluorine atom or methyl group; R 9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring (a) Δ 9 (11) when R 9 is nothing and (b) 9β,11-epoxide when R 9 is an oxygen atom; R 11 is a hydrogen or oxygen atom, two hydrogen atoms, or α- or β-hydroxyl group which makes the C-ring (a) Δ 9 (11) when R 11 is a hydrogen atom, (b) 9β,11β-epoxide when R 11 is an oxygen atom and between C 11 and R 11 is a single bond, and (c) a ketone when R 11 is an oxygen atom and between C 11 and R 11 is a double bond; R 16 is a hydrogen atom or methyl group; is a single or double bond; and ˜ indicates that the attached atom or group can be in either the a or β configurations.

Claim 25

A 17β-cyano-17α-hydroxy steroid of the formula ##STR79## and C 3 protected forms thereof where R 6 is a hydrogen or fluorine atom or methyl group; R 9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring (a) Δ 9 (11) when R 9 is nothing and (b) 9β,11-epoxide when R 9 is an oxygen atom; R 11 is a hydrogen or oxygen atom, two hydrogen atoms, or α- or β-hydroxyl group which makes the C-ring (a) Δ 9 (11) when R 11 is a hydrogen atom, (b) 9β,11β-epoxide when R 11 is an oxygen atom and between C 11 and R 11 is a single bond, and (c) a ketone when R 11 is an oxygen atom and between C 11 and R 11 is a double bond; R 16 is a hydrogen atom or methyl group; is a single or double bond; and ˜ indicates that the attached atom or group can be in either the a or β configurations.