1-Methoxymethoxy-2-(trifluoromethoxy)benzene synthesis

Yield:851341-36-1 93%

Reaction Conditions:

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

Steps:

55.55A

A solution of 2-(trifluoromethyloxy)phenol (12.0 g, 67.4 mmol) in dichloromethane (45 mL) was cooled to 5 ⁰C, and N,N-diisopropylethylamine (23.5 mL, 135 mmol) and methoxymethyl chloride (7.68 mL, 135 mmol) were added dropwise, keeping the internal temperature <15 ⁰C. The reaction mixture was warmed to ambient temperature, stirred for 15 min at ambient temperature, then 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 (13.9 g, 62.6 mmol, 93%).which was used without further purification. MS (DCI/NH₃) m/z 222 (M+H)⁺.

References:

WO2010/45401,2010,A1 Location in patent:Page/Page column 70