反应详情

温度

-40 °C

Diisopropylamine (140 g, 1.39 mol) and 800 mL dry THF were added to a dry 12 L 4 neck flask with a mechanical stirrer under nitrogen. The solution was cooled to −40° C. and n-BuLi (1.29 mol) was added slowly while keeping the inside temperature around −40° C. The mixture was stirred for 45 min at −40° C. and then cooled to −78° C. To this solution, a solution of 3-tert-butoxycarbonylamino-thiophene-2-carboxylic acid methyl ester (99 g, 0.384 mmol) in 3.2 L THF was added drop wise. The mixture was stirred for 60 min at −78° C. and then cyclohexanone (118 g, 1.19 mmol) was added in 30 seconds. The mixture was stirred for 30 min at −78° C. The reaction mixture was quenched with 0.75 L of NH4Cl (sat). The aqueous phase was extract with 0.75 L of EtOAc. Combined the organic phase and washed them with 5 L of brine, Dried over Na2SO4, filtered and evaporated to a residue to afford 115 g (84%) of 3-tert-Butoxycarbonylamino-5-(1-hydroxy-cyclohexyl)-thiophene-2-carboxylic acid methyl ester.

1. customthe inside temperature around −40° C
2. temperaturecooled to −78° C
3. stirringThe mixture was stirred for 60 min at −78° C.
4. stirringThe mixture was stirred for 30 min at −78° C
5. customThe reaction mixture was quenched with 0.75 L of NH4Cl (sat)
6. extractionThe aqueous phase was extract with 0.75 L of EtOAc
7. washwashed them with 5 L of brine
8. dry with materialDried over Na2SO4
9. filtrationfiltered
10. customevaporated to a residue