Water → Ammonia

Participants

Reaction Steps

4-(Benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol (Preparation 16, 150 mg, 0.36 mmol) was dissolved in dimethylformamide (2 ml), caesium carbonate (140 mg, 0.43 mmol) was added and stirred at room temperature for 30 minutes. tert-Butyl(7-bromoheptyl)carbamate (Prepared according to J. Med. Chem., 1994, 137, p2537-2551; 170 mg, 0.43 mmol), dissolved in dimethylformamide (1 ml), was added and heated to 70oC. After 2.5 hours caesium carbonate (70 mg, 0.22 mmol) was added and after a further 10 minutes tert-butyl(7-bromoheptyl)carbamate (70 mg, 0.18 mmol) was added. After 1 hour caesium carbonate (20 mg, 0.06 mmol) and tert-butyl(7-bromoheptyl)carbamate (35 mg, 0.09 mmol) were added and after 1 hour at 70° C. the mixture was cooled to room temperature and stirred for 3 days before the addition of water and brine were added, the mixture extracted with ethyl acetate, dried (magnesium sulphate), filtered and the solvents removed in vacuo and the residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (98/2/0.2 to 95/5/0.5 by volume) to furnish the title compound as a colourless gum, 220 mg.

Provenance & Evidence