Tetrahydrofuran → (4-Chloro-2,6-difluorophenyl)methanol

To a mixture of 4-chloro-2,6-difluoro-benzaldehyde (5.7 g, 32 mmol), tetrahydrofuran (150 mL) and ethanol (20 mL) was added sodium borohydride (1.2 g, 32 mmol) at 0° C. The mixture was stirred for 30 minutes, warmed to ambient temperature, and additional sodium borohydride (0.40 g, 11 mmol) was added to drive the reaction to completion (TLC). The mixture was concentrated in vacuo, diluted with ether and treated cautiously with 1M aqueous HCl. The aqueous phase was extracted 3× with ether, and the combined organic layers were dried over MgSO4, filtered and concentrated. Trituration of the residue with pentane afforded 4.8 g (83%) of (4-chloro-2,6-difluoro-phenyl)-methanol as a colorless solid. 1H NMR (300 MHz, CDCl3) δ7.04 (d, 2H, J=7.1 Hz), 4.73 (s, 2H) ppm.

1. customthe reaction to completion (TLC)
2. concentrationThe mixture was concentrated in vacuo
3. additiondiluted with ether
4. additiontreated cautiously with 1M aqueous HCl
5. extractionThe aqueous phase was extracted 3× with ether
6. dry with materialthe combined organic layers were dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-a87fd504fb604627a09bc3d259f1f4db

Source dataset

uspto-grants-2001_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06235764B1