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

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).

1. temperatureHeat
2. waitAfter 24 hr
3. filtrationat ambient temperature, the mixture is filtered
4. washRinse the solids with 7% H2O in acetonitrile (2×20 mL)
5. temperatureHeat the filtrate to 50° C.
6. additionadd 1N NaOH (216.1 mL)
7. concentrationConcentrate the resulting mixture under reduced pressure
8. customto remove the acetonitrile
9. temperatureAdd H2O (211 mL) and heat the solution to 70° C
10. temperatureCool to ambient temperature
11. customcollect the precipitate
12. filtrationby filtration
13. washWash with water (25 mL) and vacuum
14. customdry at 50° C. overnight

ORD-Eintrag

ord-4d66aff9e0f14201a975602180b76df6

Quelldatensatz

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08227468B2