2-Bromo-1-methoxy-4-(trifluoromethyl)benzene → HCID 57132321, compound

Participants

Reaction Conditions

Reaction Steps

2-Bromo-4-(trifluoromethyl)anisole (227 mg, 0.89 mmol), prepared according to the procedure of J. Alexander (Org. Prep. Proced. Int., 1986, 18, 213-215), was dissolved in 3.7 mL of THF and cooled in a -78° C. bath. A solution of t-butyllithium (1.0 mL, 1.7M in hexane, 1.7 mmol) was added over a period of 2 min. After 30 min., a solution of 200 mg (0.56 mmol) of (5R,6S,7S)-7-(benzyloxymethyl)-6-(4-fluorophenyl)-1-oxaspiro[4.4]nonane-3-one (prepared from methyl (5R,6S,7S)-6-(4-fluorophenyl)-3-(methylene)-1-oxaspiro[4.4]nonane-7-carboxylate (from Example 9) by DIBALH reduction, benzylation with sodium hydride and benzyl bromide, and oxidation as described in Example 6, Step C) in 1.0 mL of THF was added, and the reaction was stirred for 45 min. at -78° C. followed by warming to -35° C. over 20 min. The reaction was quenched by the addition of 10 mL of saturated aqueous ammonium chloride and partioned between 30 mL of ethyl acetate and 10 mL of water. The organic layer was washed with 10 mL of saturated aqueous sodium bicarbonate and 10 mL of saturated aqueous sodium chloride, dried over sodium sulfate, decanted, and evaporated. The crude product was purified by flash column chromatography, eluting with 1.5-5% ethyl ether in toluene to give 154 mg of the title compound.

Provenance & Evidence