Sodium borohydride → 2,2-Difluoro-2-(4-fluorophenyl)-1-methoxyethanol

Temperature

-57.5 °C

A solution of methyl difluoro(4-fluorophenyl)acetate (2.04 g, 10.0 mmol) from Step E in methanol (10.0 mL) was cooled to −60° C. Sodium borohydride (380 mg, 10.0 mmol) was added in 5 portions at 10 to 15 min. intervals. The mixture was cooled to −60 to −55° C. prior to each addition and allowed to warm to −45° C. following each addition. After the last addition, the mixture was stirred 1.25 h at −50 to −45° C. The mixture was cooled to −60° C. and quenched with 1 N aq. HCl (30 mL), with the temperature rising to −20° C. near the end of the addition. After warming to 0° C., the mixture was extracted with ether (3×20 mL). The combined ether layers were washed with water (2×20 mL), dried (sodium sulfate), decanted, and evaporated to give 1.95 g of crude 2,2-difluoro-2-(4-fluorophenyl)-1-methoxyethanol as a pale yellow oil.

1. additionto each addition
2. temperatureto warm to −45° C.
3. additioneach addition
4. additionAfter the last addition
5. temperatureThe mixture was cooled to −60° C.
6. customquenched with 1 N aq. HCl (30 mL), with the temperature
7. additionrising to −20° C. near the end of the addition
8. temperatureAfter warming to 0° C.
9. extractionthe mixture was extracted with ether (3×20 mL)
10. washThe combined ether layers were washed with water (2×20 mL)
11. dry with materialdried (sodium sulfate)
12. customdecanted
13. customevaporated

ORD record

ord-9c4ed644b09c4de99dd7daf12f90c8b3

Source dataset

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06593346B2