US4072698A
Expired / Lapsed
US
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Resolution of aminonitriles
Assignee: Pharmacia and Upjohn Co
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Filing: 1976-12-02
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Granted: 1978-02-07
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Expires: 1996-12-02
Abstract
Abstract The present invention is a chemical method for obtaining an optically pure 2-aminonitrile or a 2-aminoamide from (1) an optically impure mixture, (2) a racemic mixture, or (3) the optically pure enantiomer of the opposite configuration, in an amount greater than actually present, by use of optically active acids with a ketone or an aldehyde catalyst. Yields of greater than 70 percent of one enantiomer are obtained from racemic mixtures in very short time periods.
Inventors
- 👤 Thomas A. Hylton
- 👤 Francis L. Shenton
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-31 19:31
CPC Classifications
C; C07; C07C; C07C255/00
Claims Analysis
Total Claims: 39
Claim 1
Independent Claim
365 words
A process for producing an optically pure 2-aminonitrile enantiomer of the formula: ##STR11## where R is alkyl of 1 thru 6 carbon atoms; cycloalkyl of 3 thru 6 carbon atoms; aromatic of 6 thru 10 carbon atoms, substituted with 0 thru 3 substituents, which may be the same or different and are selected from the group consisting of alkyl of 1 thru 6 carbon atoms, hydroxyl, alkoxy where the alkyl group contains 1 thru 6 carbon atoms, cyclic alkylenedioxy where the alkylene group contains 1 thru 3 carbon atoms, halogen, trifluoromethyl, and cyano; aralkyl of 7 or 8 carbon atoms substituted with 0 thru 3 substituents, which may be the same or different and are selected from the group consisting of alkyl of 1 thru 6 carbon atoms, hydroxyl, alkoxy where the alkyl group contains 1 thru 6 carbon atoms, or cyclic alkylenedioxy where the alkylene group contains 1 thru 3 carbon atoms; 2- or 3-furyl, 2- or 3-thienyl and 2- or 3-indolylmethyl in acid salt form in an amount greater than present in an optically impure 2-aminonitrile (III) mixture which comprises contacting the optically impure 2-aminonitrile (III) mixture with an optically active acid in the presence of a compound of the formula R 1 COR 2 (IV), the methyl or ethyl actal, ketal, hemiacetal, or hemi-ketal thereof, where R 1 and R 2 may be the same or different with the proviso that both R 1 and R 2 cannot both be aromatic and where R 1 is alkyl of 1 thru 6 carbon atoms; cycloalkyl of 4 thru 6 carbon atoms; aromatic of 6 thru 10 carbon atoms, substituted with 0 thru 3 substituents selected from the group consisting of alkyl of 1 thru 6 carbon atoms, halogen, alkoxy where the alkyl group contains 1 thru 6 carbon atoms; or aralkyl of 7 or 8 carbon atoms; R 2 is hydrogen or R 1 ; and when R 2 is not hydrogen, R 1 and R 2 taken together with the attached carbon atom may form a cyclic ketone selected from the group consisting of cyclobutanone, cyclopentanone, cyclohexanone and cycloheptanone, and separating the diastereomeric acid salt of the optically pure 2-aminonitrile (III) enantiomer.
Claim 2
Dependent Claim
365 words
A process for producing an optically pure 2-aminonitrile enantiomer of the formula: ##STR11## where R is alkyl of 1 thru 6 carbon atoms; cycloalkyl of 3 thru 6 carbon atoms; aromatic of 6 thru 10 carbon atoms, substituted with 0 thru 3 substituents, which may be the same or different and are selected from the group consisting of alkyl of 1 thru 6 carbon atoms, hydroxyl, alkoxy where the alkyl group contains 1 thru 6 carbon atoms, cyclic alkylenedioxy where the alkylene group contains 1 thru 3 carbon atoms, halogen, trifluoromethyl, and cyano; aralkyl of 7 or 8 carbon atoms substituted with 0 thru 3 substituents, which may be the same or different and are selected from the group consisting of alkyl of 1 thru 6 carbon atoms, hydroxyl, alkoxy where the alkyl group contains 1 thru 6 carbon atoms, or cyclic alkylenedioxy where the alkylene group contains 1 thru 3 carbon atoms; 2- or 3-furyl, 2- or 3-thienyl and 2- or 3-indolylmethyl in acid salt form in an amount greater than present in an optically impure 2-aminonitrile (III) mixture which comprises contacting the optically impure 2-aminonitrile (III) mixture with an optically active acid in the presence of a compound of the formula R 1 COR 2 (IV), the methyl or ethyl actal, ketal, hemiacetal, or hemi-ketal thereof, where R 1 and R 2 may be the same or different with the proviso that both R 1 and R 2 cannot both be aromatic and where R 1 is alkyl of 1 thru 6 carbon atoms; cycloalkyl of 4 thru 6 carbon atoms; aromatic of 6 thru 10 carbon atoms, substituted with 0 thru 3 substituents selected from the group consisting of alkyl of 1 thru 6 carbon atoms, halogen, alkoxy where the alkyl group contains 1 thru 6 carbon atoms; or aralkyl of 7 or 8 carbon atoms; R 2 is hydrogen or R 1 ; and when R 2 is not hydrogen, R 1 and R 2 taken together with the attached carbon atom may form a cyclic ketone selected from the group consisting of cyclobutanone, cyclopentanone, cyclohexanone and cycloheptanone, and separating the diastereomeric acid salt of the optically pure 2-aminonitrile (III) enantiomer.
Claim 3
Dependent Claim
29 words
A process according to claim 1 where the 2-aminonitrile (III) is selected from the group consisting of 2-amino-2-phenylacetonitrile, 2-amino-2-(p-methoxyphenyl)acetonitrile, 2-amino-2-(p-hydroxyphenyl)acetonitrile, 2-amino-2-2-(3-chloro-4-hydroxyphenyl)acetonitrile, 2-amino-2-(2- or 3-furyl) acetonitrile or 2-amino-2-(2- or 3-thienyl)acetonitrile.
Claim 4
Dependent Claim
38 words
A process according to claim 2 where the optically active acid is selected from the group consisting of tartaric acid, diacetyl tartaric acid, dibenzoyl tartaric acid, di-p-toluyl tartaric acid, malic acid, camphoric acid, mandelic acid or menthoxyacetic acid.
Claim 5
Dependent Claim
14 words
A process according to claim 3 where the optically active acid is L-(+)-tartaric acid.
Claim 6
Dependent Claim
12 words
A process according to claim 4 wherein the 2-aminonitrile (III) is 2-amino-2-phenylacetonitrile.
Claim 7
Dependent Claim
16 words
A process according to claim 5 where the compound R 1 COR 2 (IV) is acetone.
Claim 8
Dependent Claim
12 words
A process according to claim 4 where the 2-aminonitrile (III) is 2-amino-2-(p-methoxyphenyl)acetonitrile.
Claim 9
Dependent Claim
16 words
A process according to claim 7 where the compound R 1 COR 2 (IV) is acetone.
Claim 10
Dependent Claim
11 words
A process according to claim 4 where the 2-aminonitrile is 2-amino-2-(p-hydroxyphenyl)acetonitrile.
Claim 11
Dependent Claim
15 words
A process according to claim 9 where the compound R 1 COR 2 is acetone.
Claim 12
Dependent Claim
90 words
A process for resolving a racemic 2-aminonitrile mixture to greater than 50% yield of one enantiomer of the formula: ##STR12## in acid salt form which comprises contacting the racemic 2-aminonitrile (III) with an optically active acid in the presence of a compound of the formula R 1 COR 2 (IV), the methyl or ethyl acetal, ketal, hemi-acetal, or hemi-ketal thereof, and separating the diastereomeric acid salt of the optically pure 2-aminonitrile (III) enantiomer, where R, R 1 COR 2 (IV), R 1 and R 2 are defined in claim 1.
Claim 13
Dependent Claim
27 words
A process according to claim 11 where the 2-aminonitrile (III) is selected from the group consisting of 2-amino-2-phenylacetonitrile, 2-amino-2-(p-methoxyphenyl)-acetonitrile, 2-amino-2-(p-hydroxyphenyl)acetonitrile, 2-amino-2-(3-chloro-4-hydroxyphenyl)acetonitrile, 2-amino-2-(2- or 3-furyl)acetonitrile or 2-amino-2-(2-or 3-thienyl)-acetonitrile.
Claim 14
Dependent Claim
38 words
A process according to claim 12 where the optically active acid is selected from the group consisting of tartaric acid, diacetyl tartaric acid, dibenzoyl tartaric acid, di-p-toluyl tartaric acid, malic acid, camphoric acid, mandelic acid or menthoxyacetic acid.
Claim 15
Dependent Claim
14 words
A process according to claim 13 where the optically active acid is L-(+)-tartaric acid.
Claim 16
Dependent Claim
12 words
A process according to claim 14 where the 2-aminonitrile (III) is 2-amino-2-phenylacetonitrile.
Claim 17
Dependent Claim
16 words
A process according to claim 15 where the compound R 1 COR 2 (IV) is acetone.
Claim 18
Dependent Claim
16 words
A process according to claim 15 wherein the compound R 1 COR 2 (IV) is benzaldehyde.
Claim 19
Dependent Claim
16 words
A process according to claim 15 where the compound R 1 COR 2 (IV) is 2-butanone.
Claim 20
Dependent Claim
16 words
A process according to claim 15 where the compound R 1 COR 2 (IV) is cyclohexanone.
Claim 21
Dependent Claim
16 words
A process according to claim 15 where thhe compound R 1 COR 2 (IV) is cyclopentanone.
Claim 22
Dependent Claim
16 words
A process according to claim 15 where the compound R 1 COR 2 (IV) is 2,2-dimethoxypropane.
Claim 23
Dependent Claim
16 words
A process according to claim 15 where the compound R 1 COR 2 (IV) is α-ethylisovaleraldehyde.
Claim 24
Dependent Claim
12 words
A process according to claim 14 where the 2-aminonitrile (III) is 2-amino-2-(p-methoxyphenyl)acetonitrile.
Claim 25
Dependent Claim
16 words
A process according to claim 23 where the compound R 1 COR 2 (IV) is acetone.
Claim 26
Dependent Claim
16 words
A process according to claim 23 where the compound R 1 COR 2 (IV) is benzaldehyde.
Claim 27
Dependent Claim
16 words
A process according to claim 23 where the compound R 1 COR 2 (IV) is 2-butanone.
Claim 28
Dependent Claim
12 words
A process according to claim 14 where the 2-aminonitrile (III) is 2-amino-2-(p-hydroxyphenyl)acetonitrile.
Claim 29
Dependent Claim
16 words
A process according to claim 27 where the compound R 1 COR 2 (IV) is acetone.
Claim 30
Dependent Claim
16 words
A process according to claim 27 where the compound R 1 COR 2 (IV) is benzaldehyde.
Claim 31
Dependent Claim
16 words
A process according to claim 27 where the compound R 1 COR 2 (IV) is 2-butanone.
Claim 32
Dependent Claim
88 words
A process for producing an optically pure 2-aminonitrile enantiomer of the formula: ##STR13## in acid salt form which comprises contacting the optically pure 2-aminonitrile enantiomer of the opposite configuration with an optically active acid in the presence of a compound of the formula R 1 COR 2 (IV), a methyl or ethyl acetal, ketal, hemi-acetal, or hemi-ketal thereof, and separating the diasteromeric acid salt of the optically pure 2-aminoninitrile (III) enantiomer, where R, R 1 COR 2 (IV), R 1 and R 2 are defined in claim 1.
Claim 33
Dependent Claim
28 words
A process according to claim 31 where the 2-aminonitrile (III) is selected from the group consisting of 2-amino-2-phenylacetonitrile, 2-amino-2-(p-methoxyphenyl)-acetonitrile, 2-amino-2-(p-hydroxyphenyl)acetonitrile, 2-amino-2-(3-chloro-4-hydroxyphenyl)acetonitrile, 2-amino-2-(2- or 3-furyl)acetonitrile or 2-amino-2-(2- or 3-thienyl)-acetnoitrile.
Claim 34
Dependent Claim
38 words
A process according to claim 32 where the optically active acid is selected from the group consisting of tartaric acid, diacetyl tartaric acid, dibenzoyl tartaric acid, di-p-toluyl tartaric acid, malic acid, camphoric acid, mandelic acid or menthoxyacetic acid.
Claim 35
Dependent Claim
14 words
A process according to claim 33 where the optically active acid is L-(+)-tartaric acid.
Claim 36
Dependent Claim
12 words
A process according to claim 34 where the 2-aminonitrile (III) is 2-amino-2-phenylacetonitrile.
Claim 37
Dependent Claim
16 words
A process according to claim 35 where the compound R 1 COR 2 (IV) is acetone.
Claim 38
Dependent Claim
25 words
A process for resolving racemic 2-amino-2-phenylacetonitrile to greater than 50% yield of D-(+)-2-amino-2-phenylacetonitrile-hydrogen-L-(+)-tartrate which comprises contacting racemic 2-amino-2-phenylacetonitrile with optically active L-(+)-tartaric acid and acetone.
Claim 39
Dependent Claim
25 words
A process for resolving racemic 2-amino-2-phenylacetonitrile to greater than 50% yield of D-(+)-2-amino-2-phenylacetonitrile-hydrogen-L-(+)-tartrate which comprises contacting racemic 2-amino-2-phenylacetonitrile with optically active L-(+)-tartaric acid and acetone.
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) | 1981-02-06 | 1981-08-08 | 1982-02-07 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-02-06 | 1985-08-08 | 1986-02-07 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-02-06 | 1989-08-08 | 1990-02-07 | $7700.00 | Window Closed / Lapsed |