Sodium borohydride → 2-Chloro-6-(trifluoromethyl)-4-pyridinemethanol

Temperature

0 °C

Sodium tetrahydroborate (74 mg, 2.0 mmol) was added to a solution of ethyl 2-chloro-6-(trifluoromethyl)isonicotinate (0.50 g, 2.0 mmol, Anichem) in ethanol (17 mL) at 0° C. The mixture was stirred at 0° C. for one hour, then was allowed to warm to room temperature and stir for 2 hours. The mixture was recooled in an ice bath and was quenched by the dropwise addition of 4.0 mL 1N HCl. The pH was then adjusted to 7 by the addition of saturated sodium bicarbonate solution. The reaction was further diluted with water, and then was extracted with EtOAc. The extract was washed with brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography on silica gel, eluting with a gradient from 0-40% EtOAc in Hexanes afforded product as an oil (0.33 g, 79%). 1H NMR (300 MHz, CDCl3) δ 7.61 (s, 1H), 7.56 (s, 1H), 4.84 (d, J=5.2 Hz, 2H), 2.20 (t, J=5.6 Hz, 1H); LCMS (M+H)+: 212.1.

1. temperatureto warm to room temperature
2. stirringstir for 2 hours
3. customThe mixture was recooled in an ice bath
4. customwas quenched by the dropwise addition of 4.0 mL 1N HCl
5. additionThe pH was then adjusted to 7 by the addition of saturated sodium bicarbonate solution
6. additionThe reaction was further diluted with water
7. extractionwas extracted with EtOAc
8. washThe extract was washed with brine
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. washFlash chromatography on silica gel, eluting with a gradient from 0-40% EtOAc in Hexanes afforded product as an oil (0.33 g, 79%)

ORD record

ord-1758f518ca7748c088b700e12f8c7cbc

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933085B2