Hydrochloric Acid → 12-(Methanesulfonyl)-3-methoxy-5,8,8a,9,10,11,12,12a,13,13a-decahydro-6H-isoquinolino[2,1-g][1,6]naphthyridine--hydrogen chloride (1/1)

Participants

Reaction Conditions

Reaction Steps

A slurry of 4.894 Kg of (8aS,12aS,13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a, 13,13a-decahydroisoquino[2,1-g][1,6]naphthyridin-8-one (7) in 60 Kg of tetrahydrofuran was stirred with 1.103 Kg of sodium borohydride at about 10° C. This mixture was maintained at 10° C. while 5.836 Kg of boron trifluoride etherate was added. Upon completion of the addition the reaction mixture was refluxed for 30 minutes, cooled to 20° C., and 67 litres of 1N hydrochloric acid added cautiously. The majority of the solvent was then removed by distillation at atmospheric pressure, the residue cooled to below 30° C. and aqueous 6N sodium hydroxide solution added until the pH reached 12.2 (about 35 litres). The reaction mixture was then extracted with methylene chloride, and the combined extracts washed with water. The solvent was removed by distillation at atmospheric pressure, replacing the methylene chloride with ethanol until the pot temperature reached 78° C. The solution was then cooled to about 70° C. and concentrated aqueous hydrochloric acid (1.3 litres) was added. The slurry was stirred at about 70° C. for 10 minutes, cooled to 20° C. and then stood for 12 hours The product was filtered, washed with 33 Kg of cold ethanol and dried under vacuum at 40°-45° C., giving (8aR,12aS,13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a,13,13a-decahydro-8H-isoquino[2,1-g][1,6]naphthyridine hydrochloride, m.p. 257°-258° C.

Provenance & Evidence