Diethyl Ether → (+)-β-Amino-3,4-difluoro-α,α-dimethylbenzeneethanol

Temperature

0 °C

Into a well-stirred solution of methyl 2-amino-2-(3,4-difluorophenyl)acetate (10.5 g, 52.19 mmol) in anhydrous ether (200 mL) at 0° C. a solution of methylmagnesium bromide (3 M, 87 mL, 261 mmol) in ether was added over 10 minutes. The reaction mixture was stirred at 0° C. for 2.5 h and allowed to warm to room temperature. After 12 h, the reaction mixture was carefully poured onto a mixture of ice (300 g) and saturated aqueous ammonium chloride (50 g). The ether layer was separated and the aqueous layer was extracted with more ether (4×200 mL). The combined extracts were dried with magnesium sulfate and the solvent evaporated. The crude product was purified by column chromatography on silica gel using chloroform/methanol/2M ammonia in methanol (1000:20:10, 1000:40:20, 1000:80:40) as the eluent to give the product as an oil (6.5 g, 62% yield) which was used in the next step without further purification.

1. temperatureto warm to room temperature
2. waitAfter 12 h
3. customThe ether layer was separated
4. extractionthe aqueous layer was extracted with more ether (4×200 mL)
5. dry with materialThe combined extracts were dried with magnesium sulfate
6. customthe solvent evaporated
7. customThe crude product was purified by column chromatography on silica gel

ORD record

ord-7ddb65a92df744959f9345716a361b75

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067534B1