反应详情

To a solution of 2,5-dimethylphenylacetic acid (5.45 g, 27.4 mmol) in DMF (80 mL) is added diisopropylethylamine (85.4 mL, 411.32 mmol), followed by O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (12.8 g, 32.9 mmol) at 0° C. After stirring 15 min at RT, 2-piperidin-4-yl-thiazole-4-carboxylic acid ethyl ester (6.59 g, 27.4 mmol) is added to the reaction mixture. After stirring overnight at RT, solvent is evaporated and the resulting yellow oil is dissolved in ethylacetate (500 mL), washed with aqueous saturated sodium bicarbonate solution (500 mL) and the aqueous phase is re-extracted with ethylacetate (100 mL). The combined organic layers are washed with 0.5M HCl solution (400 mL) and brine (400 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure to give 2-{1-[2-(2,5-dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazole-4-carboxylic acid ethyl ester (10.46 g, 98%), which can be used in the next step without further purification. 1H-NMR (400 MHz, CDCl3): δ=1.41 (t, 3H), 1.52-1.82 (m, 2H), 2.10-2.22 (m, 2H), 2.25 (s, 3H), 2.30 (s, 3H), 2.73-2.86 (m, 1H), 3.08-3.22 (m, 1H), 3.29-3.40 (m, 1H), 3.68 (s, 2H), 3.8-3.95 (m, 1H), 4.38-4.42 (q, 2H), 4.73-4.88 (m, 1H), 6.96 (s, 1H), 6.98-7.01 (d, 1H), 7.08 (d, 1H), 8.10 (s, 1H). MS: m/z=387 (M+1).

1. stirringAfter stirring overnight at RT
2. customsolvent is evaporated
3. dissolutionthe resulting yellow oil is dissolved in ethylacetate (500 mL)
4. washwashed with aqueous saturated sodium bicarbonate solution (500 mL)
5. extractionthe aqueous phase is re-extracted with ethylacetate (100 mL)
6. washThe combined organic layers are washed with 0.5M HCl solution (400 mL) and brine (400 mL)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. customevaporated under reduced pressure