2-Methylbenzenesulfonic acid → HCID 69522022, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-[4-(benzyloxy)-3-methylphenyl]ethanone (intermediate 8, 1.15 g) in dry tetrahydrofuran (15 ml) at −78° C. was treated dropwise with lithium diisopropylamide (2.6 ml of 2M solution in heptane/tetrahydrofuran/ethylbenzene) under nitrogen. The reaction mixture was warmed to 0° C. for 30 minutes. The mixture was cooled to −78° C. and 4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carbaldehyde (intermediate 2, 1.08 g) in dry tetrahydrofuran (15 ml) was added drop-wise at −78° C. and the reaction mixture stirred at 21° C. for 2 hours. Acetic acid (4 ml) in dry tetrahydrofuran (4 ml) was added followed by toluenesulphonic acid (0.1 g) and the reaction mixture was heated at 50° C. for 1 hour and then concentrated. The residue was partitioned between saturated bicarbonate solution and ethyl acetate; the aqueous layer separated and extracted thrice more with ethyl acetate. The organic solutions were combined and were dried with brine and over magnesium sulfate and concentrated. The product isolated after evaporation of the solvent was further purified by flash chromatography using cyclohexane:ethyl acetate (6:1) as eluent to give the title compound as a yellow solid.

Provenance & Evidence