2-METHOXY-4-(TRIFLUOROMETHYL)BENZOYL CHLORIDE synthesis

Yield:-

Reaction Conditions:

with thionyl chloride;N,N-dimethyl-formamide in toluene at 80; for 3 h;

Steps:

V.1

Step 1 : 2-(2-Methoxy-4-trifluoromethyl-phenyl)-4,4-dimethyl-4,5-dihvdro-oxazoleTo a solution of 24.98 g (113 mmol) 4-(trifluoromethyl)-2-methoxy-benzoic acid in 220 ml toluene were added 82 ml (1.13 mol) thionyl chloride and 5 drops dimethylformamide. The mixture was heated to 80⁰C for 3h. Then the reaction mixture was concentrated at 50 °C/10 mbar. The remaining acid chloride, 27.9 g of a light yellow liquid, was dissolved in 160 mldichloromethane, cooled to 0 ⁰C and a solution of 20.34 g (228 mmol) 2-amino-2-methyl- propan-1-ol in 60 ml dichloromethane added. The mixture was allowed to stir at ambient temperature for 16 h. The off-white suspension was diluted with water, the aqueous phase evaporated and the organic phase extracted 3 times with ethyl acetate. The combined organic layers were dried over Na₂SO₄, filtered and concentrated. The crude product, 33.2g N-(I- hydroxy-l,l-dimethyl-ethyl)-2-methoxy-4-trifluoro-methyl-benzamide, a light yellow oil was dissolved in 220 ml dichloromethane and cooled to 0 ⁰C. Then 24.7 ml (340 mmol) thionyl chloride was added drop-wise and the resulting light yellow solution stirred at ambient temperature for 16 h. Then the pH was adjusted to 10 by addition of saturated aqueous Na₂CO₃ solution. The aqueous layer was separated and extracted 3 times with tert-butyl methyl ether. The combined organic phases were washed twice with brine, dried over Na₂SO₄, filtered and concentrated. 2-(2-Methoxy-4-trifluoromethyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole was obtained as light yellow oil which was used without further purification: MS (ISP): 274.1((M+H)⁺).

References:

WO2011/23667,2011,A1 Location in patent:Page/Page column 32