反应详情

To a flask containing 60% NaH in mineral oil (213 mg, 5.32 mmol) under nitrogen was added THF (31.7 mL) and carbonic acid, dimethyl ester (0.448 mL, 5.32 mmol). The mixture was heated to 60 degrees and a solution of 1-(4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazol-5-yl)ethanone (875 mg, 2.66 mmol) in THF (12.7 mL) was then added. The mixture was heated at 60 degrees for 1 hour. The reaction was cooled and quenched with methanol (5 mL), then saturated NH4Cl (10 mL). The organic solvents were concentrated in vacuo, and the aqueous residue was diluted with water (10 mL) and extracted with ethyl acetate (2×20 mL). The combined organic layers were dried, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (EA/DCM=0/100→40/60) to give 253 mg (25% yield) of the title compound as an oil. LC/MS (FA) ES+ 387, 389. 1H NMR (300 MHz, CDCl3) δ: 8.76-8.74 (m, 2H), 7.83-7.81 (m, 2H), 7.35-7.32 (m, 2H), 7.26-7.23 (m, 2H), 4.53 (s, 2H), 3.89 (s, 2H), 3.77 (s, 3H).

1. temperatureThe mixture was heated to 60 degrees
2. temperatureThe mixture was heated at 60 degrees for 1 hour
3. temperatureThe reaction was cooled
4. customquenched with methanol (5 mL)
5. concentrationThe organic solvents were concentrated in vacuo
6. additionthe aqueous residue was diluted with water (10 mL)
7. extractionextracted with ethyl acetate (2×20 mL)
8. customThe combined organic layers were dried
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was purified by silica gel chromatography (EA/DCM=0/100→40/60)