US4564706A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Process for the preparation of propargyl amines
Assignee: Chinoin Private Co Ltd
•
Filing: 1983-07-14
•
Granted: 1986-01-14
•
Expires: 2003-07-14
Abstract
Abstract The invention relates to a new process for the preparation of propargyl ammonium chlorides of the Formula I ##STR1## by alkaline decomposition of the d-tartarate of the 1-isomer of an amine of the Formula II ##STR2## and subsequent reaction of the amine of the Formula II with a halide of the Formula III X--CH.sub.2 --C.tbd.CH (III) in the presence of an organic solvent, alkali and water in which in Formulae II and III respectively, n is 1 or 0 and X stands for halogen which comprises reacting the d-tartarate of the 1-isomer of an amine of the Formula II in aqueous suspension with an alkali, dissolving the base of the Formula II, thus set free without isolation in a water non-miscible organic solvent and reacting the same in the said phase with a halide of the Formula III, and thereafter--preferably after separating the aqueous layer--reacting the mixture which contains the amines of the Formulae II and IV ##STR3## in the organic phase in the presence of water with an organic acid or a solution which has a pH value of 1.5-6 and consists of an inorganic acid and water, thus dissolving in the two-phase mixture formed the salt of the amine of the Formula II in the aqueous layer and selectively separating the amine of the Formula II from the amine of the Formula IV, and thereafter adding after the separation of the phases hydrogen chloride to the amine of the Formula IV being in the organic phase and thus precipitating the salt of the Formula I. The compounds of Formula I are known pharmaceutical active ingredients. The advantage of the process of the present invention that it is highly economical and enables the recovery of the starting materials on large scale production too.
Inventors
- 👤 Zoltan Ecsery
- 👤 Eva Somfai
- 👤 Judit Hermann nee Voros
- 👤 Lajos Nagy
- 👤 Gabor Szabo
- 👤 Otto Orban
- 👤 Laslzo Arvai
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 14:42
CPC Classifications
C; C07; C07C; C07C209/00; C07C209/04; C07C209/06; C07C209/08
Claims Analysis
Total Claims: 8
Claim 1
Independent Claim
245 words
A process for the preparation of a salt of the Formula (I) ##STR7## wherein n=0 or 1 which comprises the steps of: (a) dissolving a free base of the Formula (II) ##STR8## in a water, non-miscible organic solvent and propargylating said free base with a compound of the Formula (III) X--CH.sub.2 --C.tbd.CH wherein X is halo, in the presence of an alkali and water at 40°-70° C. to yield a mixture of the unreacted free base of the Formula (II) and a free base of the Formula (IV) ##STR9## in a two-phase system containing an organic phase and a first aqueous phase; (b) separating the organic phase which contains the mixture of the free base of the Formula (II) and the free base of the Formula (IV) from the first aqueous phase; (c) treating the organic phase containing the mixture of the free base of the Formula (II) and the free base of the Formula (IV) with water and an amount of acid sufficient to adjust the pH of the solution to 6.5 to 7 to selectively dissolve, in a second two-phase system thus formed, a salt of the compound of the Formula (II) in the aqueous phase while the free base of the Formula (IV) remains in the organic phase; (d) separating the aqueous phase from the organic phase; and (e) treating the organic phase containing the free base of the Formula (IV) with hydrogen chloride to precipitate the salt of the Formula (I).
Claim 2
Dependent Claim
245 words
A process for the preparation of a salt of the Formula (I) ##STR7## wherein n=0 or 1 which comprises the steps of: (a) dissolving a free base of the Formula (II) ##STR8## in a water, non-miscible organic solvent and propargylating said free base with a compound of the Formula (III) X--CH.sub.2 --C.tbd.CH wherein X is halo, in the presence of an alkali and water at 40°-70° C. to yield a mixture of the unreacted free base of the Formula (II) and a free base of the Formula (IV) ##STR9## in a two-phase system containing an organic phase and a first aqueous phase; (b) separating the organic phase which contains the mixture of the free base of the Formula (II) and the free base of the Formula (IV) from the first aqueous phase; (c) treating the organic phase containing the mixture of the free base of the Formula (II) and the free base of the Formula (IV) with water and an amount of acid sufficient to adjust the pH of the solution to 6.5 to 7 to selectively dissolve, in a second two-phase system thus formed, a salt of the compound of the Formula (II) in the aqueous phase while the free base of the Formula (IV) remains in the organic phase; (d) separating the aqueous phase from the organic phase; and (e) treating the organic phase containing the free base of the Formula (IV) with hydrogen chloride to precipitate the salt of the Formula (I).
Claim 3
Dependent Claim
32 words
The process defined in claim 1, wherein in step (a), the reaction of the compounds of the Formula (II) and (III) is carried out in the presence of a phase transfer catalyst.
Claim 4
Dependent Claim
22 words
The process according to claim 1, wherein in step (a), the water non-miscible organic solvent is benzene, toluene, dichloroethane, or diisopropyl ether.
Claim 5
Dependent Claim
14 words
The process defined in claim 2, wherein the phase transfer catalyst is N-benzyl-N,N,N-triethyl-ammonium chloride.
Claim 6
Dependent Claim
21 words
The process defined in claim 1, wherein in step (a), the propargylation is carried out at a temperature of 60° C.
Claim 7
Dependent Claim
280 words
A process for the preparation of a salt of the Formula (I) ##STR10## wherein n=0 or 1 which comprises the steps of: (a) alkali decomposing an aqueous suspension of the D-tartarate of the l-isomer of a compound of the Formula (II) ##STR11## with an alkali, to obtain the free base of the Formula (II) without isolation; (b) dissolving the free base of the Formula (II) in a water, non-miscible organic solvent and propargylating said free base with a compound of the Formula (III) X--CH.sub.2 --C.tbd.CH wherein X is halo, in the presence of an alkali and water at 40° to 70° C. to yield a mixture of the unreacted free base of the Formula (II) and a free base of the Formula (IV) ##STR12## in a two-phase system containing an organic phase and a first aqueous phase; (c) separating the organic phase which contains the mixture of the free base of the Formula (II) and the free base of the Formula (IV) from the first aqueous phase; (d) treating the organic phase containing the mixture of the free base of the Formula (II) and the free base of the Formula (IV) with water and an amount of acid sufficient to adjust the pH of the solution to 6.5 to 7 to selectively dissolve, in a second two-phase system thus formed, a salt of the compound of the Formula (II) in the aqueous phase while the free base of the Formula (IV) remains in the organic phase; (e) separating the aqueous phase from the organic phase; and (f) treating the organic phase containing the free base of the Formula (IV) with hydrogen chloride to precipitate the salt of the Formula (I).
Claim 8
Dependent Claim
280 words
A process for the preparation of a salt of the Formula (I) ##STR10## wherein n=0 or 1 which comprises the steps of: (a) alkali decomposing an aqueous suspension of the D-tartarate of the l-isomer of a compound of the Formula (II) ##STR11## with an alkali, to obtain the free base of the Formula (II) without isolation; (b) dissolving the free base of the Formula (II) in a water, non-miscible organic solvent and propargylating said free base with a compound of the Formula (III) X--CH.sub.2 --C.tbd.CH wherein X is halo, in the presence of an alkali and water at 40° to 70° C. to yield a mixture of the unreacted free base of the Formula (II) and a free base of the Formula (IV) ##STR12## in a two-phase system containing an organic phase and a first aqueous phase; (c) separating the organic phase which contains the mixture of the free base of the Formula (II) and the free base of the Formula (IV) from the first aqueous phase; (d) treating the organic phase containing the mixture of the free base of the Formula (II) and the free base of the Formula (IV) with water and an amount of acid sufficient to adjust the pH of the solution to 6.5 to 7 to selectively dissolve, in a second two-phase system thus formed, a salt of the compound of the Formula (II) in the aqueous phase while the free base of the Formula (IV) remains in the organic phase; (e) separating the aqueous phase from the organic phase; and (f) treating the organic phase containing the free base of the Formula (IV) with hydrogen chloride to precipitate the salt of the Formula (I).
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1989-01-13 | 1989-07-15 | 1990-01-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-01-13 | 1993-07-15 | 1994-01-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-01-13 | 1997-07-15 | 1998-01-14 | $7700.00 | Window Closed / Lapsed |