Acetonitrile → (3R,4S)-4-Amino-6-bromochroman-3-ol

Participants

Reaction Steps

Heat a mixture of racemic-trans-4-amino-6-bromochroman-3-ol (21.1 g, 86.4 mmol), D-(+)-camphoric acid (17.3 g, 86.4 mmol), acetonitrile (633 mL) and water (47.6 mL) to 70-75° C. and stir for 10 min. The solution is allowed to cool to ambient temperature over 4 hr. After 24 hr. at ambient temperature, the mixture is filtered. Rinse the solids with 7% H2O in acetonitrile (2×20 mL). Heat the filtrate to 50° C. and add 1N NaOH (216.1 mL). Concentrate the resulting mixture under reduced pressure to remove the acetonitrile. Add H2O (211 mL) and heat the solution to 70° C. Cool to ambient temperature and collect the precipitate by filtration. Wash with water (25 mL) and vacuum dry at 50° C. overnight to obtain the title compound as an off-white solid (9.8 g, 46.4% of 50% theoretical weight, 98.7% ee).

Provenance & Evidence