反应详情

温度

-78 °C

To a solution of 8-methanesulfonyl-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one (described in example 208, step A) (50 mg, 13 mmol) in THF (3 mL) at −78° C. was added nBuLi (1.6M solution in heptane, 80 uL, 13 mmol), and the reaction mixture was stirred at −78° C. for 10 mins. Then a solution of 4-bromo-butyryl chloride (15 uL 0.13 mmol) in THF (1 mL) was added and the reaction mixture was stirred for a further 30 mins at −78° C. and then another 2 equivalents of nBuLi were added and the reaction mixture was warmed to room temperature. The reaction was quenched with water and extracted with ethyl acetate. The organic phases were combined, dried (Na2SO4), filtered and concentrated in vacuo to give a crude residue was purified by flash column chromatography (4:1 AcOEt/heptane) to yield 8-[dihydro-furan-(2Z)-ylidenemethanesulfonyl]-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one (15 mg, 26%) as a white solid. MS (ESI): 461.4 (MH+).

1. stirringthe reaction mixture was stirred for a further 30 mins at −78° C.
2. temperaturethe reaction mixture was warmed to room temperature
3. customThe reaction was quenched with water
4. extractionextracted with ethyl acetate
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give a crude residue
9. customwas purified by flash column chromatography (4:1 AcOEt/heptane)