反应详情

To a solution of the above-prepared 1-(4-methoxymethyl-2-phenyl-thiazol-5-yl)-ethanone (5.22 g, 21.12 mmole, 1.0 eq) in dry THF (100 ml) at −15° C. was added dropwise a solution of 1.0M potassium t-butoxide in THF (31.7 ml, 31.7 mmole, 1.5 eq) and the suspension stirred at room temperature under nitrogen for one hour. Diethyl oxalate (4.4 ml, 31.7 mmole, 1.5 eq) was added, the brown suspension diluted with additional THF (60 ml) and allowed to stir at room temperature for 30 minutes. The mixture was quenched by adding glacial acetic acid (3.2 ml, 2.6 eq). THF was removed in vacuo, and the residual oil was dissolved in absolute ethanol (175 ml) and treated with hydrazine monohydrate(1.4 ml, 30 mmole, 1.4 eq). This mixture was heated at 70° C. for 3 hours. The resulting yellow suspension was concentrated in vacuo leaving a residual oil that was dissolved in ethyl acetate. The organic phase was washed with water, saturated NaHCO3 and brine, then dried over anhydrous sodium sulfate and concentrated in vacuo to give a yellow oily solid. Silica gel chromatography using a gradient elution of (9:1)-(4:1) hexanes-ethyl acetate provided a yellow solid which was triturated with hexanes, filtered and driedin vacuo to give 3.69 g (51%)of the title compound as an off-white solid. 1H NMR(CDCl3): δ 1.4 (t, 3H), 3.5 (s, 3H), 4.4 (q, 2H), 4.8 (s, 2H), 7.0 (s, 1H), 7.4 (m, 3H), 7.9-8.0 (m, 2H).

1. stirringto stir at room temperature for 30 minutes
2. customThe mixture was quenched
3. customTHF was removed in vacuo
4. dissolutionthe residual oil was dissolved in absolute ethanol (175 ml)
5. temperatureThis mixture was heated at 70° C. for 3 hours
6. concentrationThe resulting yellow suspension was concentrated in vacuo
7. customleaving a residual oil that
8. washThe organic phase was washed with water, saturated NaHCO3 and brine
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated in vacuo
11. customto give a yellow oily solid
12. washa gradient elution of (9:1)-(4:1) hexanes-ethyl acetate
13. customprovided a yellow solid which
14. customwas triturated with hexanes
15. filtrationfiltered