Patent ID: 6040480
Filing Date: 2000-03-21
Classification: A61P,C07C,C07D

Abstract:
A process for the preparation of an amino alcohol compound of formula (V-i): ##STR76## comprising (1) adding a toluene solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to a toluene solution of a compound of formula (III-i): ##STR77## while maintaining a reaction temperature of about 0.degree. C. to about 10.degree. C.;(2) maintaining the reaction temperature at about 0.degree. C. for about 1 hour to form a toluene slurry of 2,3-dichloro-5,6-dicyano-1,4-dihydroxybenzene and a compound of formula (IV-i): ##STR78## (3) filtering the slurry to remove the 2,3-dichloro-5,6-dicyano-1,4-dihydroxybenzene;(4) washing the 2,3-dichloro-5,6-dicyano-1,4-dihydroxybenzene waste cake with toluene;(5) combining the filtrate and toluene washings;(6) concentrating in vacuo the filtrate and toluene solution of the compound of formula (IV-i) with methanol to remove most of the toluene;(7) adding dropwise to the compound of formula (IV-i) in methanol at a temperature of about 40.degree. C. to about 45.degree. C. an aqueous solution of sodium hydroxide forming a clear solution of the amino alcohol and p-methoxy-benzaldehyde;(8) adding dropwise to the clear solution of the amino alcohol a solution of NaBH.sub.4 in an aqueous solution of sodium hydroxide maintaining a reaction temperature of about 40.degree. C. to about 45.degree. C.;(9) stirring the reaction mixture for about 30 minutes;(10) neutralizing the reaction with glacial acetic acid to a pH of about 8 to about 9;(11) adding water to form a slurry;(12) cooling the slurry to about -15.degree. C. to about 0.degree. C. for about 1 hour; and(13) filtering the cooled slurry of the amino alcohol and washing with water to give the crude crystalline amino alcohol as a pale yellow solid.