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US 4,066,658 AGranted
Resolution of D,L-dehydroproline
AssigneeHoffmann-La Roche Inc.
InventorArthur Martin Felix
Life of this patent
Estimating the term…
Abstract
D,L-3,4-dehydroproline is resolved in high optical yield by conversion to its N-protected derivative, treatment with R(+)alpha-methyl-p-nitrobenzylamine to form the diastereomeric salts, fractional crystallization, decomposition of the L-R salt and regeneration of the secondary amine group. The product L-3,4-dehydroproline obtained in extremely high optical purity is useful as an inhibitor of collagen synthesis.
Claims6
A method for the preparation of L-3,4-dehydroproline comprising in combination the steps of:
- A. treating N-protected D,L-3,4-dehydroproline with R(+)-alpha-methyl-p-nitrobenzylamine so as to form the corresponding diastereomeric salt, the said N-protecting group being selected from conventional N-protecting groups which can be deblocked without racemization of the resolved compound;
- B. selectively crystallizing the N-protected L-3,4-dehydroproline (R)-alpha-methyl-p-nitrophenethyl ammonium salt from solution;
- C. decomposing the aforesaid diastereomeric salt with cold aqueous weak acid so as to produce N-protected-L-3,4-dehydroproline;
- and
- D. removing the N-protecting group under conditions which do not cause racemization thereby yielding L-3,4-dehydroproline.
2 more elements
A method for the preparation of L-3,4-dehydroproline and D-3,4-dehydroproline comprising in combination the steps of:
- A. treating N-protected D,L-3,4-dehydroproline with R(+)-alpha-methyl-p-nitrobenzylamine so as to form the corresponding diastereomeric salt, the said N-protecting group being selected from conventional N-protecting groups which can be deblocked without racemization of the resolved compound;
- B. selectively crystallizing the N-protected L-3,4-dehydroproline-(R)-alpha-methyl-p-nitrophenethyl-ammonium salt from solution;
- C. decomposing the aforesaid diastereomeric salt with cold weak aqueous organic acid so as to produce N-protected L-3,4-dehydroproline;
- D. removing the N-protecting group under conditions which do not cause racemization thereby yielding L-3,4-dehydroproline;
- E. treating the mother liquors from step (B) with S-(-)-alpha-methyl-p-nitrobenzylamine so as to produce N-protected D-3,4-dehydroproline-(S)-alpha-methyl-p-nitrophenethyl-ammonium salt;
- F. decomposing the diastereomeric salt of step (E) with cold weak aqueous acid so as to produce N-protected D-3,4-dehydroproline;
- and
- G. removing the N-protecting group under conditions which do not cause racemization thereby yielding D-3,4-dehydroproline.
5 more elements
Dependencies are inferred from the claim text.