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) δ 7.04 (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-886920096a77494ea49f64c496266577

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07405218B2