反应详情

温度

12.5 °C

A mixture of tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (limiting reagent) and 2-isopropylthiazole-4-carboxylic acid (1.1 molar equivalents) was suspended in 2-MeTHF (10 volumes) and cooled to 10-15° C. Triethylamine (7.2 molar equivalents) was added in portions at 10-15° C. The thick suspension was cooled to 5-10° C. and T3P (1.3 molar equivalents of a 1.57M solution in THF) was added dropwise at 5-10° C. over 0.5 hr. The reaction mixture was allowed to warm to ambient temperature (35 min) and stirred for 2.5 hr. The mixture was diluted with water (10 volumes, 5° C. exotherm) and the mixture vigorously stirred; the aqueous (pH 10) was separated and extracted with 2-MeTHF (2×2 volumes). The combined organics were washed with saturated aq sodium bicarbonate soln (2 volumes) and water (2×2 volumes). The organic phase was evaporated and azeotroped with MeCN (2×2 volumes) to give a brown gum, which was dried at 35° C. in vacuo for 24 hr. Yield: 89% of theoretical.

1. temperatureThe thick suspension was cooled to 5-10° C.
2. temperatureto warm to ambient temperature (35 min)
3. stirringthe mixture vigorously stirred
4. customthe aqueous (pH 10) was separated
5. extractionextracted with 2-MeTHF (2×2 volumes)
6. washThe combined organics were washed with saturated aq sodium bicarbonate soln (2 volumes) and water (2×2 volumes)
7. customThe organic phase was evaporated
8. customazeotroped with MeCN (2×2 volumes)
9. customto give a brown gum, which
10. customwas dried at 35° C. in vacuo for 24 hr