Cyclopropanecarboxaldehyde → 8-(2-Cyclopropyl-2-hydroxy-ethanesulfonyl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one

温度

0 °C

To a solution of 8-methanesulfonyl-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one (76 mg, 0.19 mmol) in THF at −78° C. was added n-BuLi (1.6M, 145 uL, 0.23 mmol) dropwise. The reaction mixture was stirred for 5 min followed by the addition of a solution of cyclopropanecarbaldehyde (54 mg, 0.78 mmol) in THF (500 uL) at −78° C. The dry ice bath was removed and the reaction mixture was warmed to 0° C. and stirring was continued for a further 30 min. The reaction mixture was quenched with AcOH (20 uL) and was then concentrated to dryness under reduced pressure. The crude residue was partitioned between ethyl acetate and water and the organic layer was then washed with brine, dried with Na2SO4, filtered and concentrated in vacuo to give a crude residue which was purified by flash column chromatography to afford 8-(2-cyclopropyl-2-hydroxy-ethanesulfonyl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one (42 mg, 47%) as a white solid. MS (ESI): 463.2 (MH+)

1. customThe dry ice bath was removed
2. stirringstirring
3. waitwas continued for a further 30 min
4. customThe reaction mixture was quenched with AcOH (20 uL)
5. concentrationwas then concentrated to dryness under reduced pressure
6. customThe crude residue was partitioned between ethyl acetate and water
7. washthe organic layer was then washed with brine
8. dry with materialdried with Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give a crude residue which
12. customwas purified by flash column chromatography

ORDレコード

ord-25cce12b00b7474d9674c344d9d49b2f

出典データセット

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08329904B2