Hydrochloric Acid → tert-butyl [(2S)-2-{[4-bromo-2-(hydroxymethyl)thiophen-3-yl]oxy}propyl]carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 4-bromo-3-{(1S)-2-[(tert-butoxycarbonyl)amino]-1-methylethoxy}thiophene-2-carboxylate (15.36 g) in THF-MeOH (5:1, 180 mL) was added 8 N aqueous sodium hydroxide solution (7.5 mL) at room temperature, and the mixture was stirred at 50° C. for 1 hr. The reaction solution was cooled to room temperature, neutralized with 6 N hydrochloric acid (10 mL), and extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. To a solution (250 ml) of the residue in THF were added isobutyl chloroformate (5.6 mL) and triethylamine (6.5 ml), and the mixture was stirred at room temperature for 30 min. The reaction solution was filtered, a solution (10 ml) of sodium borohydride (4.42 g) in water was added to the filtrate, and the mixture was stirred at room temperature for 30 min. Saturated aqueous ammonium solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient; 10→25% ethyl acetate/hexane) to give the title compound (12.82 g, 90%) as a colorless oil.

Provenance & Evidence