海萝胶 → (R)-1-(5-bromopyridin-3-yl)ethanol

温度

0 °C

A solution of (S)-(−)-α,α-diphenyl-2-pyrrolidinemethanol (253 mg, 1 mmol) and trimethyl borate (0.135 mL, 1.2 mmol) in tetrahydrofuran (10 mL) was stirred at room temperature for 1 hour after which time borane-methylsulfide complex (10 mL, 2M in tetrahydrofuran, 20 mmol) was added in one portion and the mixture cooled to 0° C. A solution of 3-acetyl-5-bromopyridine (2 g, 10 mmol) in tetrahydrofuran (10 mL) was added dropwise over 2 hours at 0° C. and then the mixture was allowed to warm to room temperature and was stirred overnight. After this time dilute aqueous hydrochloric acid (2M, 90 mL) was added with initial cooling and the mixture was stirred at room temperature for 2 hours. Dimethyl sulfide and tetrahydrofuran were removed under reduced pressure and the resulting yellow solution was basified to pH 11 with aqueous ammonia, extracted with ethyl acetate (3×50 mL) and the extracts washed with brine (50 mL), dried (MgSO4) and concentrated under reduced pressure to give (1R)-1-(5-bromopyridin-3-yl)ethanol (1.9 g) in acceptable purity.

1. additionwas added in one portion
2. temperatureto warm to room temperature
3. temperaturewith initial cooling
4. stirringthe mixture was stirred at room temperature for 2 hours
5. customDimethyl sulfide and tetrahydrofuran were removed under reduced pressure
6. extractionextracted with ethyl acetate (3×50 mL)
7. washthe extracts washed with brine (50 mL)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated under reduced pressure

ORD记录

ord-4cba110b59c5404ab60e6a841263e205

来源数据集

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

专利号

US08461161B2