反应详情

温度

0 °C

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.

1. temperatureThe mixture was cooled to −78° C.
2. temperaturethe reaction mixture was heated at 50° C. for 1 hour
3. concentrationconcentrated
4. customThe residue was partitioned between saturated bicarbonate solution and ethyl acetate
5. customthe aqueous layer separated
6. extractionextracted thrice more with ethyl acetate
7. dry with materialwere dried with brine and over magnesium sulfate
8. concentrationconcentrated
9. customThe product isolated
10. customafter evaporation of the solvent
11. customwas further purified by flash chromatography