Yield:336628-65-0 92%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in dichloromethane at 5 - 20;

Steps:

42.42A

A solution of 2-(trifluoromethyl)phenol (12.0 g, 74.0 mmol) in dichloromethane (49 niL) was cooled to 5 ⁰C, and N,N-diisopropylethylamine (25.9 niL, 148 mmol) and methoxymethyl chloride (8.43 mL, 111 mmol) were added dropwise, keeping the internal temperature <15 ⁰C. After stirring for 15 min at ambient temperature, the reaction mixture was diluted with MTBE (250 mL) and washed with 2N HCl (2 x 50 mL), water (50 mL), 2N NaOH (2 x 30 mL), water (30 mL), and brine (30 mL). The organic portion was dried (Na₂SO₄), filtered, and concentrated to give the title compound (14.1 g, 68.4 mmol, 92%) which was used without further purification. MS (DCI/NH₃) m/z 207 (M+H)⁺.

References:

WO2010/45401,2010,A1 Location in patent:Page/Page column 62-63