Methanol → Methyl 4-fluoro-3-methylbenzoate

Temperature

35 °C

To a solution of 4-fluoro-3-methyl-benzoic acid (27.4 g, 178.0 mmol) in methanol (200 mL) was slowly added thionyl chloride (17.8 mL, 243.3 mmol). The solution was stirred at 35° C. for 7 hours. The solution was allowed to cool to room temperature and concentrated in vacuo to an oil. This oil was dissolved in EtOAc (75 mL) and washed sequentially with saturated aqueous sodium bicarbonate solution (2×75 mL) and brine solution (1×75 mL). The organic layer was separated and dried over sodium sulfate, filtered and concentrated in vacuo to provide methyl 4-fluoro-3-methyl-benzoate (25.4 g, 85%) as a red oil. ESI-MS m/z calc. 168.0. Found 169.2 (M+1)+; Retention time: 1.48 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.92-7.88 (m, 1H), 7.88-7.83 (m, 1H), 7.04 (t, J=8.9 Hz, 1H), 3.90 (s, 3H), 2.31 (d, J=2.0 Hz, 3H).

1. temperatureto cool to room temperature
2. concentrationconcentrated in vacuo to an oil
3. dissolutionThis oil was dissolved in EtOAc (75 mL)
4. washwashed sequentially with saturated aqueous sodium bicarbonate solution (2×75 mL) and brine solution (1×75 mL)
5. customThe organic layer was separated
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-a5bd32c636f446a4b6758feb2de44494

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08828996B2