Claims
- 1. A process comprising the step of crystallizing out of solution the salt of an optically active base with an optically active form of penicillamine having at least one of the hydrogen atoms of the mercapto group and the amino group protected as a compound of the formula: ##EQU5## where R.sub.1 and R.sub.2 are both methyl or R.sub.1 and R.sub.2 are joined together to form the pentamethylene group and Ac is formyl employing the D,L racemate form of said protected penicillamine and 1-norephedrine free of d-norephedrine and precipitating the salt of the D-form of the protected penicillamine and the 1-norephedrine.
- 2. A process according to claim 1 wherein the solvent is water, alcohol, aliphatic hydrocarbon, halogenated aliphatic hydrocarbon, dioxane, a ketone, an ester or an aromatic hydrocarbon.
- 3. A process according to claim 1, wherein R.sub.1 and R.sub.2 are both methyl.
- 4. A process according to claim 3, wherein there are used 0.1 to 3 moles of 1-norephedrine per mole of racemate.
- 5. A process according to claim 4 wherein there are used 0.5 to 1.1 mole of the 1-norephedrine.
- 6. A process according to claim 1, wherein R.sub.1 and R.sub.2 are joined together to form the pentamethylene group.
- 7. A process according to claim 6, wherein there are used 0.1 to 3 moles of 1-norephedrine per mole of racemate.
- 8. A process according to claim 7 wherein there are used 0.5 to 1.1 moles of the 1-norephedrine.
- 9. A process according to claim 1 wherein R.sub.1 and R.sub.2 are both methyl, there are used 0.1 to 3 moles of 1-norephedrine per mole of racemate and the solvent is ethyl acetate, isopropyl alcohol, toluene, acetone, dioxane, benzene or carbon tetrachloride.
- 10. A process comprising the step of crystallizing out of solution the salt of an optically active base with an optically active form of penicillamine having at least one of the hydrogen atoms of the mercapto group and the amino group protected as a compound of the formula: ##EQU6## in which R.sub.1 and R.sub.2 are both methyl or R.sub.1 and R.sub.2 are joined together to form the pentamethylene group and Ac is formyl, employing the D,L racemate form of said protected penicillamine and a salt of 1-norephedrine free of d-norephedrine and precipitating the salt of the D-form of the protected penicillamine and 1-norephedrine.
- 11. A process according to claim 10 wherein the salt of 1-norephedrine is a salt of an organic acid.
- 12. A process according to claim 11 wherein the salt of 1-norephedrine is a salt of a sulfonic acid or a carboxylic acid.
- 13. A process according to claim 12 wherein the acid is unsubstituted or is substituted by hydroxy, --OR, --SH, --SR, halogen, --NH.sub.2, --NHR or ##EQU7## where R is alkyl.
- 14. A process according to claim 13 wherein the acid is unsubstituted or is substituted by hydroxy, --OR, --SH, --SR, or halogen.
- 15. A process according to claim 14 wherein the acid is unsubstituted or substituted with --OH.
- 16. A process according to claim 15 wherein the acid is unsubstituted.
- 17. A process according to claim 16 wherein the acid is an alkanoic acid, phenylalkanoic acid, alkenoic acid, phenylalkenoic acid, hydroxyalkanoic acid, phenylhydroxyalkanoic acid, hydroxyaryl carboxylic acid, aryl carboxylic acid or heterocyclic carboxylic acid.
- 18. A process according to claim 17 wherein the acid has 1 to 3 carboxylic acid groups.
- 19. A process according to claim 18 wherein the alkanoic acid had 1 to 6 carbon atoms, the hydroxylakanoic acid has 2 to 6 carbon atoms, the phenylalkanoic acid has 2 to 3 carbon atoms in the alkanoic acid portion of the molecule, the alkenoic acid has 3 to 4 carbon atoms, the phenylalkenoic acid has 3 carbon atoms in the alkenoic acid portion of the molecule, the phenylhydroxyalkanoic acid has 3 carbon atoms in the hydroxyalkanoic acid portion of the the molecule, the aryl carboxylic acid is a benzene mono or dicarboxylic acid, the hydroxyaryl carboxylic acid is hydroxybenzoic acid and the heterocyclic carboxylic acid has the carboxylic group attached to a carbon atom of the heterocyclic ring, the heterocyclic ring containing 5 to 6 carbon atoms, said heterocyclic ring having 1 to 2 hetero atoms, the hetero atoms being selected from the group consisting of oxygen, nitrogen and sulfur, the carboxyl group being the sole substituent on the ring.
- 20. A process according to claim 19 wherein the acid is formic acid, acetic acid or propionic acid.
- 21. A process according to claim 20 wherein the acid is benzene sulfonic acid or toluene sulfonic acid.
- 22. A process according to claim 18, wherein R.sub.1 and R.sub.2 are both methyl.
- 23. A process according to claim 18, wherein R.sub.1 and R.sub.2 are joined together and are pentamethylene.
- 24. A process according to claim 10 wherein the salt is the salt of an alkanoic acid, phenylalkanoic acid, alkenoic acid, phenylalkenoic acid, hydroxyalkanoic acid, phenylhydroxyalkanoic acid, hydroxyaryl carboxylic acid, aryl carboxylic acid, alkane sulfonic acid, arylsulfonic acid or heterocyclic carboxylic acid where the heterocyclic group is the thiophene, thiazole, furan or pyridine or indole group.
- 25. A process according to claim 24 wherein the salt is the 1-norephedrine salt of acetic acid, propionic acid, maleic acid, benzoic acid, formic acid, phenylpropionic acid, citric acid or benzenesulfonic acid.
- 26. A process according to claim 10 wherein the salt is a salt of an alkanoic acid, phenylalkanoic acid, alkenoic acid, phenylalkenoic acid, hydroxyalkanoic acid, phenylhydroxyalkanoic acid, hydroxyaryl carboxylic acid, aryl carboxylic acid, alkanesulfonic acid, arylsulfonic acid, sulfuric acid, hydrochloric acid, hydrobromic acid, nitric acid or phosphoric acid.
- 27. A process according to claim 10 wherein the salt is a salt of isobutyric acid, n-valeric acid, isovaleric acid, trimethylacetic acid, lactic acid, oxalic acid, malonic acid, adipic acid, maleic acid, succinic acid, tartaric acid, citric acid, formic acid, acetic acid, propionic acid, phenylacetic acid, mandelic acid, cinnamic acid, 3-phenyl propionic acid, phthalic acid, terephthalic acid, salicylic acid, benzoic acid, thiophene-2-carboxylic acid, thiazole-4-carboxylic acid, furane-2-carboxylic acid picolinic acid, isonictinic acid, methanesulfonic acid, methane trisulfonic acid, propane-2-sulfonic acid, p-toluenesulfonic acid or benzene sulfonic acid.
Parent Case Info
The present application is a continuation-in-part of application Ser. No. 276,530, filed July 31, 1972 and now abandoned and application Ser. No. 419,473, filed Nov. 27, 1973 and now abandoned, the entire disclosures of which are hereby incorporated by reference and relied upon.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
1867274 |
Manske |
Jul 1932 |
|
2450784 |
Duffin et al. |
Oct 1948 |
|
Non-Patent Literature Citations (1)
Entry |
Stewart, Stereo Chemistry, Langmans, Green & Co., London, 1919, pp. 40-42. |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
276530 |
Jul 1972 |
|