反应详情

Sodium hydride (86.0 mg, 2.15 mmol, 60% dispersion in mineral oil) was added to a solution of (8R)-8-(3,5-difluorophenyl)-8-methyl-6,9-diazaspiro[4.5]decan-10-one (502 mg, 1.791 mmol, described in Intermediate 1) in 5 ml of DMF. When the gas evolution had ceased, propargyl bromide (320 mg, 2.15 mmol, 80 wt % in toluene) was added to the solution at ambient temperature. After 16 hours, the reaction was quenched with water (20 mL) and extracted with CH2Cl2 (3×20 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified on silica gel, eluting with a gradient of CH2Cl2:ethyl acetate—98:2 to 50:50. The clean fractions were concentrated in vacuo to yield the title compound. MS: m/z=319 (M+1).

1. customthe reaction was quenched with water (20 mL)
2. extractionextracted with CH2Cl2 (3×20 ml)
3. dry with materialThe combined organic layers were dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe crude product was purified on silica gel
7. washeluting with a gradient of CH2Cl2
8. concentrationThe clean fractions were concentrated in vacuo