Process for making piloloctam and derivatives thereof

Details Process for making piloloctam and derivatives thereof Process for making piloloctam and derivatives thereof

1996-07-18

1997-10-07

Shah, Mukund J.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C07D207267

Patent

active

056750196

ABSTRACT:
A process of preparing lactam derivatives of pilocarpine is disclosed. The process involves condensation of a dihydroxybutene and alkyl orthoester to form a lactone intermediate which is oxidized to trans-pilopic acid. This lactone ring is reacted with a benzylamine and the benzyl group removed with a novel dissolving metal reduction mixture to yield the key intermediate IV ##STR1## which can be elaborated to pilolactam through a known sequence of steps.

REFERENCES:
patent: 3470197 (1969-09-01), VanDyke, Jr.
patent: 5055467 (1991-10-01), Albaugh
patent: 5198545 (1993-03-01), Albaugh
patent: 5264449 (1993-11-01), Albaugh
patent: 5453434 (1995-09-01), Albaugh et al.
DeGraw, J.I., "Prostaglandins, An Improved Synthesis of Pilocarpine," Tetrahedron., vol. 28, 1972, pp. 967-972.
Koda et al, "Synthesis of Analogs related to Pilocarpine", Journal of Pharmaceutical Sciences, Dec. 1973, vol. 62, No. 12, pp. 2021-2023.
Sauerberg et al, "Cyclic Carbamate Analogues of Pilocarpine", J. Med. Chem. 1989, 32, pp. 1322-1326.
Kondo et al, "Synthesis of y-Lactones By The Condensation of 2-Alkene-1, 4-Diols With Orthocarboxylic Esters", Chemistry Letters, pp. 741-742, 1974.
Noordam et al, "Stereoselective synthesis (+)-pilocarpine, an imidazole alkaloid used in ophthalmology", Recl. Trav. Chim. Pays-Bas 98, pp. 425-470.
Dey, A.N., "The Jaborandi Alkaloids. Part I. The Synthesis of Homo-and isoHomo-pilopic Acids and of r-Pilocarpidine and r-isoPilocarpidine by New Methods and the Resolution of r-Pilocarpine, S. Chem. Soc.", (1937), pp. 1057-1065.
Birch et al, "Reduction by Metal-Ammonia Solutions and Related Reagents", Advanced Organic Chemistry, No. 8, pp. 1-65 (1972).
Benkeser et al, "Reduction of Organic Compounds by Lithium in Low Molecular Weight Amines. VII. The Preparation of Dihydroaromatics. A Comparison of the Lithium-Amine and Birch Reduction Systems", Journal of Organic Chemistry, 28, pp. 1094-1096, 1972.
Kaiser, E.M., "A Comparison of Methods Using Lithium/Amine and Birch Reduction Systems", Synthesis, 1972, pp. 391-415.

Affiliated with

Also associated with

Rating

Process for making piloloctam and derivatives thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for making piloloctam and derivatives thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for making piloloctam and derivatives thereof will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2358522