US3887606A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Process for the preparation of DL-phenylglycine esters
Assignee: Glaxo Laboratories Ltd
•
Filing: 1972-06-02
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Granted: 1975-06-03
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Expires: 1992-06-02
Abstract
Abstract A process for the resolution of DL-phenylglycine esters in which said ester is treated with (+)-tartaric acid in the presence of a mixture of solvents of different polarities, one of which is an alkanol having 1-4 carbon atoms, and the (+)-hermitartrate of the D-phenylglycine ester is selectively crystallised therefrom. Dphenylglycine and/or its salts may be obtained by hydrolysis of the ester thus formed. D-phenylglycine is a valuable intermediate in the synthesis of antibiotics of the penicillin and cephalosporin types. The present invention provides a relatively cheap, high yield process for the production of optically active esters of phenylglycine by way of their diastereoisomeric salts and for the production of optically active phenylglycine therefrom. Novel D-phenylglycine esters and salts are disclosed.
Inventors
- 👤 Gordon Hanley Phillipps
- 👤 Leslie Stephenson
- 👤 Albert Roy Cooksey
- 👤 John Colin Clark
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 11:34
CPC Classifications
C; C07; C07D; C07D401/00; C07D401/02; C07D401/04
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
109 words
A process for the resolution of a DL-phenylglycine ester of the formula: C6H5CH.NH2.CO2R where R represents an alkyl group with 1 to 6 carbon atoms or a cycloalkyl group withh 5 or 6 carbon atoms, which comprises treating said DL-phenylglycine ester with (+)-tartaric acid at a temperature of from 15* to 60*C in the presence of a mixture of solvents of different polarities one of which is an alkanol having 1-4 carbon atoms, the said (+)-tartaric acid being used in a stoichiometric amount or in an excess up to 100 percent, and selectively crystallising the (+)-hemitartrate of the D-phenylglycine ester therefrom at a temperature of from -20* to +60*C.
Claim 2
Dependent Claim
109 words
A process for the resolution of a DL-phenylglycine ester of the formula: C6H5CH.NH2.CO2R where R represents an alkyl group with 1 to 6 carbon atoms or a cycloalkyl group withh 5 or 6 carbon atoms, which comprises treating said DL-phenylglycine ester with (+)-tartaric acid at a temperature of from 15* to 60*C in the presence of a mixture of solvents of different polarities one of which is an alkanol having 1-4 carbon atoms, the said (+)-tartaric acid being used in a stoichiometric amount or in an excess up to 100 percent, and selectively crystallising the (+)-hemitartrate of the D-phenylglycine ester therefrom at a temperature of from -20* to +60*C.
Claim 3
Dependent Claim
12 words
A PROCESS FOR THE RESOLUTION OF A DL-PHENYLGLYCINE ESTER OF THE FORMULA:
Claim 4
Dependent Claim
12 words
A PROCESS FOR THE RESOLUTION OF A DL-PHENYLGLYCINE ESTER OF THE FORMULA:
Claim 5
Dependent Claim
26 words
A process as claimed in claim 1 wherein a DL-phenylglycine ester is used in which R represents a methyl, ethyl, isopropyl, butyl, isobutyl or cyclohexyl group.
Claim 6
Dependent Claim
38 words
A process as claimed in claim 1 wherein said mixture of solvents contains a solvent selected from among the following: water, sulphoxide solvents, nitrile solvents, amide solvents, ester solvents, carboxylic acid solvents and hydrocarbon and chlorinated hydrocarbon solvents.
Claim 7
Dependent Claim
12 words
A process as claimed in claim 1 wherein the alkanol is methanol.
Claim 8
Dependent Claim
12 words
A process as claimed in claim 1 wherein the alkanol is ethanol.
Claim 9
Dependent Claim
14 words
A process as claimed in claim 1 wherein said mixture of solvents contains water.
Claim 10
Dependent Claim
13 words
A process as claimed in claim 3 wherein said sulphoxide solvent comprises dimethylsulphoxide.
Claim 11
Dependent Claim
29 words
A process as claimed in claim 1 for the resolution of ethyl DL-phenylglycinate wherein the resolution is effected in the presence of aqueous methanol or aqueous ethanol as solvent.
Claim 12
Dependent Claim
32 words
A process as claimed in claim 1 for the resolution of methyl DL-phenylglycinate wherein the resolution is effected in the presence of aqueous ethanol or aqueous industrial methylated spirit (I.M.S.) as solvent.
Claim 13
Dependent Claim
33 words
A process as claimed in claim 1 wherein the (+)-hemitartrate of the D-phenylglycine ester thus obtained is hydrolysed in an aqueous solution of a strong acid, whereby a salt of D-phenylglycine is obtained.
Claim 14
Dependent Claim
31 words
A process as claimed in claim 10 wherein the pH of the hydrolysis mixture, containing the salt of D-phenylglycine thus formed, is Adjusted to the range 4-9 whereby D-phenylglycine is obtained.
Claim 15
Dependent Claim
144 words
A process for the resolution of a DL-phenylglycine ester of the formula C6H5CH.NH2.CO2R where R represents an alkyl group with 1 to 6 carbon atoms or a cycloalkyl group with 5 or 6 carbon atoms, which comprises the resolution steps of treating said DL-phenylglycine ester with (+)-tartaric acid at a temperature of from 15* to 60*C in the presence of a mixture of solvents of different polarities one of which is an alkanol having 1 to 4 carbon atoms, the said (+)-tartaric acid being used in a stoichiometric amount or in an excess up to 100 percent, and selectively crystallising the (+)-hemitartrate of the D-phenylglycine ester therefrom at a temperature of from -20* to +60*C; separating said crystallized (+)-hemitartrate from the remaining L-phenylglycine ester or salt thereof, racemising said remaining L-phenylglycine ester or salt thereof and resolving said racemate by repeating said resolution steps.
Claim 16
Dependent Claim
144 words
A process for the resolution of a DL-phenylglycine ester of the formula C6H5CH.NH2.CO2R where R represents an alkyl group with 1 to 6 carbon atoms or a cycloalkyl group with 5 or 6 carbon atoms, which comprises the resolution steps of treating said DL-phenylglycine ester with (+)-tartaric acid at a temperature of from 15* to 60*C in the presence of a mixture of solvents of different polarities one of which is an alkanol having 1 to 4 carbon atoms, the said (+)-tartaric acid being used in a stoichiometric amount or in an excess up to 100 percent, and selectively crystallising the (+)-hemitartrate of the D-phenylglycine ester therefrom at a temperature of from -20* to +60*C; separating said crystallized (+)-hemitartrate from the remaining L-phenylglycine ester or salt thereof, racemising said remaining L-phenylglycine ester or salt thereof and resolving said racemate by repeating said resolution steps.
Claim 17
Dependent Claim
37 words
A process as claimed in claim 12 in which racemisation is effected by heating the L-phenylglycine ester or salt alone or in solution, either in the solvent mixture used for resolution or in a different solvent medium.
Claim 18
Dependent Claim
27 words
A process as claimed in claim 13 in which, in order to racemise any L-phenylglycine ester, a base or a weak acid is added to the solution.
Claim 19
Dependent Claim
16 words
A process as claimed in claim 12 in which said racemisation takes place simultaneously with resolution.
Claim 20
Dependent Claim
6 words
A compound of the general formula:
Claim 21
Dependent Claim
6 words
A compound of the general formula:
Claim 22
Dependent Claim
41 words
A compound as claimed in claim 16 selected from the group consisting of D-phenylglycine methyl ester (+)-hemitartrate in substantially optically pure form; D-phenylglycine ethyl ester (+)-hemitartrate in substantially optically pure form; and D-phenylglycine isopropyl ester (+)-hemitartrate in substantially optically pure form.
References Cited (Backward Citations)
US2750404A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1978-06-02 | 1978-12-02 | 1979-06-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1982-06-02 | 1982-12-02 | 1983-06-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1986-06-02 | 1986-12-02 | 1987-06-03 | $7700.00 | Window Closed / Lapsed |