Ethyl 2-Fluoro-5-Methylbenzoate synthesis

Yield:496841-90-8 95%

Reaction Conditions:

with sulfuric acid for 2 h;Reflux;

Steps:

17.A Ethyl 2-fluoro-5-methylbenzoate (17A-2).

To a stirred solution of 2-fluoro-5-methylbenzoic acid 17A-1 (2 g, 12.9 mmol) in EtOH (20 mL) was added H₂S0₄ (0.1 mL, catalytic) at 0 °C and the reaction was refluxed for 2 hr. The reaction mixture was concentrated, and to the residue was added ice cold water (100 mL) and extracted with EtOAc (3 X 200 mL), The combined organic layers were washed with water (2 X 200 mL), brine (150 mL), dried over Na₂S0₄ and concentrated. The residue was purified by flash column chromatography (100- 200 silica) using 15% EtOAc/hexanes to afford 17A-2 (2.2 g, 12.08 mmol, 95% yield) as a colorless thick liquid. MS = 183.1 [M+H]⁺.

References:

WO2016/154241,2016,A1 Location in patent:Paragraph 548; 549