Methanol → Methyl 5-chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoate

To a solution of 5-chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoic acid (1.14 g, 3.98 mmol) in anhydrous tetrahydrofuran (50 mL) was added 1,1′-carbonyldiimidazole (1.71 g, 10.50 mmol). The solution was heated to reflux under a nitrogen atmosphere for 1 hours and cooled to ambient temperature. To the solution was added anhydrous methanol (0.49 mL, 12.00 mmol) and 1,8-diazabicycloundec-7-ene (1.8 mL, 12.00 mmol). The solution was stirred at ambient temperature for 4 h, then diluted with ethyl acetate (150 mL) and washed with 1 M hydrochloric acid (2×150 mL), brine (150 mL), dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford the title compound as an off-white solid (1.05 g, 87%): 1H NMR (300 MHz, CDCl3) δ 7.99 (d, J=7.6 Hz, 1H), 6.74 (d, J=12.0 Hz, 1H), 4.79 (br s, 1H), 3.89 (s, 3H), 2.79-2.68 (m, 2H), 2.39-2.31 (m, 4H), 2.13-2.02 (m, 2H); MS (ES+) m/z 300.9 (M+1).

1. temperatureThe solution was heated
2. temperatureto reflux under a nitrogen atmosphere for 1 hours
3. washwashed with 1 M hydrochloric acid (2×150 mL), brine (150 mL)
4. dry with materialdried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-b5868c6d638540a4a6c41004fee0c517

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952169B2