Sodium Carbonate → Azd 7009

Participants

Reaction Conditions

Reaction Steps

Aqueous sodium carbonate solution (1M, 53 mL) was added to a solution of [2-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)-ethyl]-carbamic acid tert-butyl ester 2,4,6-trimethylbenzenesulfonic acid salt (50.0 g) in water (100 mL). Solid 4-[(2S)-oxiranylmethoxy]benzonitrile (19.1 g) was added and was rinsed into the reaction flask with water (50 mL). The reaction was heated to 75° C. for 3 hours and then left to stir at ambient temperature overnight. Toluene (350 mL) was added followed by aqueous sodium hydroxide (2M, 90 mL). The mixture was stirred for 5 minutes and then the phases were separated. The aqueous phase was discarded and the toluene phase washed with aqueous citric acid (10% w/v, 180 mL). The toluene phase was discarded. MIBC (240 mL) and aqueous sodium hydroxide (5M, 180 mL) were added to the citric acid phase. After mixing well the phases were separated and the aqueous discarded. The MIBC was washed with aqueous sodium chloride (20% w/v, 50 mL). The MIBC was concentrated under vacuum at <55° C. Solvent was collected (water 13 mL, MIBC 29 mL). The MIBC solution was cooled to ambient temperature and filtered, washing through with MIBC (50 mL). Solvent (152 mL) was distilled under vacuum at <66° C. and then distillation was stopped. IPE (360 mL) was added causing the temperature to fall from 65° C. to 37° C. After stirring for 15 minutes T fell by 2° C. to 35° C. and crystallisation started. The mixture was left to cool to ambient temperature overnight with stirring. The mixture was cooled to 5° C. and the product collected by filtration. The solid was washed on the filter with IPE (150 mL) and sucked dry. Further drying in vacuo at 55° C. gave the title compound as a white solid (41.2 g, 87%).

Provenance & Evidence