Sodium Hydroxide → 2-(Difluoromethoxy)-3-fluorobenzoic acid

温度

50 °C

A mixture of methyl 3-fluoro-2-hydroxy-benzoate (1.5 g, 8.8 mmol), 2-chloro-2,2-difluoro-acetic acid (1.62 g, 1.05 mL, 10.6 mmol) and potassium carbonate (1.46 g, 10.6 mmol) were heated in DMF (5 mL) at 120° C. for 5 hours. The reaction mixture was diluted with water (20 mL) and extracted with ether (2×10 mL). The organics were separated and washed sequentially with water (5 mL) and brine solution (5 mL). The organics were dried (MgSO4) and concentrated in vacuo to give residue which was purified by silica gel column chromatography using 0-30% EtOAc/hexanes as eluent to give methyl 2-(difluoromethoxy)-3-fluorobenzoate (0.8 g, 39%). To methyl 2-(difluoromethoxy)-3-fluorobenzoate (0.8 g, 3.64 mmol) was added 12% aq. NaOH (3 mL) and the reaction mixture was heated at 50° C. for 1 hour. The aqueous layer was extracted with 1:1 ether/hexane (2×5 mL). The aqueous layer was acidified to pH 1 with 6 N HCl solution to give a suspension. The solid was filtered and washed with water, then dried in vacuo to give 2-(difluoromethoxy)-3-fluoro-benzoic acid (555 mg, 31%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J=7.8 Hz, 1H), 7.43 (dd, J=13.1, 4.8 Hz, 1H), 7.35 (td, J=8.1, 4.9 Hz, 1H), 6.68 (t, J=74.4 Hz, 1H).

1. extractionThe aqueous layer was extracted with 1:1 ether/hexane (2×5 mL)
2. customto give a suspension
3. filtrationThe solid was filtered
4. washwashed with water
5. customdried in vacuo

ORDレコード

ord-3b7ea92c68ac4ac7a9b6dd0c3615731b

出典データセット

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09181273B2