反应详情

温度

0 °C

Triphosgene (8.22 g) is dissolved in dry THF (345 ml) under argon atmosphere. The solution is cooled to 0° C. and a solution of methyl 3-amino-5-bromothiophene-2-carboxylate (19.8 g) in dry THF (173 ml) is added dropwise keeping the temperature below 10° C. The mixture is stirred for 14 h at RT. The reaction mixture is cooled to 0° C. again and a solution of tert-butyl 4-aminopiperidine-1-carboxylate (17.0 g) in dry THF (173 ml) is added within 15 min keeping the temperature below 10° C. After 15 min at 0° C. and additional 3 h at RT water (495 ml) and saturated aqueous sodium chloride solution (124 ml) are added. The organic layer is separated and the aqueous layer is extracted with THF three times (124 ml each). The combined organic layers are washed with half concentrated aqueous sodium chloride solution three times (250 ml each) and with saturated aqueous sodium chloride solution (250 ml) once. After drying over sodium sulfate all volatile materials are removed in vacuo to yield the title compound as a solid which is used without further purification.

1. customthe temperature below 10° C
2. temperatureThe reaction mixture is cooled to 0° C. again
3. customthe temperature below 10° C
4. waitAfter 15 min at 0° C.
5. customThe organic layer is separated
6. extractionthe aqueous layer is extracted with THF three times (124 ml each)
7. washThe combined organic layers are washed with half concentrated aqueous sodium chloride solution three times (250 ml each) and with saturated aqueous sodium chloride solution (250 ml) once
8. dry with materialAfter drying over sodium sulfate all volatile materials
9. customare removed in vacuo