Sodium Azide → (1R*,2R*,5S*,6R*)-6-Acetamidoazido-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane

Participants

Reaction Steps

(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carboxylic acid (free base of Example 53; 377 mg, 0.67 mmol) was dissolved in dichloromethane (10 ml) and dimethylformamide (2 drops) and the mixture cooled to 0° C. then oxalyl chloride (0.063 ml, 0.72 mmol) added. The mixture was then left to warm to room temperature and stirred for 2 hours. The mixture was concentrated in vacuo then carried through crude. Acid chloride (389 mg, 0.67 mmol) was taken up in dichloromethane (10 ml) and sodium azide (48 mg, 0.74 mmol) added and the mixture stirred at room temperature for 3 days. A further 48 mg of sodium azide was added and the mixture further stirred overnight. The reaction mixture was then concentrated in vacuo and carried through crude. The isocyanate (394 mg, 0.70 mmol) was dissolved in THF (3 ml) and water (3 ml) and the mixture refluxed for 4 hours. The reaction mixture was then extracted with ethyl acetate (×2), dried (MgSO4) and concentrated in vacuo to give the title compound as a beige solid (307 mg, 82%).

Provenance & Evidence