METHOD FOR PRODUCING ENANTIOMER-FREE N-METHYL-N- [(1S)-1-PHENYL- 2-((3S)- 3-HYDROXYPYRROLIDINE- 1-YL)ETHYL]- 2,2-DIPHENYL ACETAMIDE

• Main Authors: BUDAK JENS, STEIN INGEBORG, BATHE ANDREAS, HELFERT BERND, ACKERMANN KARL-AUGUST, GOTTSCHLICH RUDOLF
• Format: Patent
• Language: English; Polish
• Published: 29.10.2010
• Subjects: APPARATUS THEREFOR; CHEMISTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Production of N-methyl-N-[(1S)-1-phenyl-2-((3S)-3-hydroxypyrrolidino)ethyl]-2,2-diphenylacetamide (Ia) or N-methyl-N-[(1R)-1-phenyl-2-((3R)-3-hydroxypyrrolidino)ethyl]-2,2-diphenylacetamide (Ib) comprises (a) reacting the corresponding enantiomer of an N-substituted phenylglycine derivative with an optionally O-protected 3-hydroxypyrrolidine derivative, (b) reducing the product to convert the N-substituent to methyl and remove any protecting group, and (c) reacting with an activated diphenylacetic acid derivative. Production of N-methyl-N-[(1S)-1-phenyl-2-((3S)-3-hydroxypyrrolidino)ethyl]-2,2-diphenylacetamide (Ia) or N-methyl-N-[(1R)-1-phenyl-2-((3R)-3-hydroxypyrrolidino)ethyl]-2,2-diphenylacetamide (Ib) comprises (a) reacting the corresponding enantiomer of an N-substituted phenylglycine derivative of formula (II) with an optionally O-protected 3-hydroxypyrrolidine derivative of formula (III), (b) reducing the product of formula (IV), and (c) reacting the product of formula (V) with an activated diphenylacetic acid derivative of formula (VI) to give a product of formula (Ia/Ib): [Image] [Image] [Image] [Image] R : H, OR 1> or SR 1>; R 1>A, aryl, heteroaryl, Si(R 3>) 3 or COR 3>; R 3>H, A, aryl or heteroaryl; A : 1-6C alkyl; M : H, alkali(ne earth) metal, NH 4 or alkylammonium; R 2>H, A, aryl, heteroaryl, Si(R 3>) 3 or COR 3>; R 4>halogen, OA or OCOA. An independent claim is also included for compounds referred to as N-methyl-N-[(1S)-1-phenyl-2-((3S)-3-hydroxypyrrolidino)ethane] and N-methyl-N-[(1R)-1-phenyl-2-((3R)-3-hydroxypyrrolidino)ethane] useful as intermediates for (Ia) and (Ib). ACTIVITY : Antiinflammatory; analgesic; diuretic. MECHANISM OF ACTION : None given.