Trimethylsilyldiazomethane → 4-Bromo-2-fluoro-benzoic acid methyl ester

To a solution of 4-bromo-2-fluorobenzoic acid (2.0 g, 9.1 mmol) in THF (24 mL) and methanol (6 mL) at 0° C. was added a solution of (trimethylsilyl)diazomethane in hexanes (2.0 M, 5.46 mL, 10.9 mmol). The yellow solution was allowed to gradually warm to room temperature over 1 h. The volatile materials were removed and the residue was treated with aqueous hydrochloric acid (1 M). The aqueous mixture was extracted with ethyl acetate. The organic extract was dried over magnesium sulfate, filtered, and concentrated to provide crude methyl 4-bromo-2-fluorobenzoate (2.7 g, quantitative yield). This material was used in the subsequent step without further purification. 1H NMR (400 MHz, CDCl3): 7.85-7.81 (m, 1H), 7.38-7.33 (m, 2H), 3.93 (s, 3H); MS (EI) for C8H6BrFO2: 232, 234 (MH+).

1. customThe volatile materials were removed
2. additionthe residue was treated with aqueous hydrochloric acid (1 M)
3. extractionThe aqueous mixture was extracted with ethyl acetate
4. extractionThe organic extract
5. dry with materialwas dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated

ORD record

ord-392c27c8127f4e33bb00730ccc392041

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08012956B2