Chloride → Tert-butyl 3-bromo-5-(2,2-difluoro-1-hydroxyethyl)benzoate

To a solution of tert-butyl 3,5-dibromobenzoate (18.43 g, 54.9 mmol) in tetrahydrofuran (137 mL) at 0° C. was added isopropylmagnessium chloride (2.0 M in THF; 46.6 mL, 93 mmol). The reaction mixture was warmed to ambient temperature. The reaction was monitor by LC-MS for disappearance of tert-butyl 3,5-dibromobenzoate. The mixture was cooled back to 0° C. and ethyl difluoroacetate (13.7 mL, 137 mmol) was added. The mixture was stirred at 0° C. for 1 h, then warmed to ambient temperature. After 18 h, methanol and saturated ammonium chloride were added and the mixture was concentrated to remove organic solvents. Water was added and the mixture was extracted with dichloromethane (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→75% hexanes/ethyl acetate) gave the title compound (4.04 g).

1. temperatureThe mixture was cooled back to 0° C.
2. temperaturewarmed to ambient temperature
3. waitAfter 18 h
4. concentrationthe mixture was concentrated
5. customto remove organic solvents
6. additionWater was added
7. extractionthe mixture was extracted with dichloromethane (3×)
8. washThe combined organic extracts were washed with brine
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customPurification by silica gel chromatography (100% hexanes→75% hexanes/ethyl acetate)

ORD record

ord-b480398ee0e94a85aa1c5726147fa84f

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08247401B2