反应详情

(S)-(1-Formyl-3-methyl-butyl)-carbamic acid tert-butyl ester (0.39 mg, 1.8 mmol) and 1-bis(4-fluorophenyl)methyl piperazine (0.50 g, 1.7 mmol) were dissolved in 1% HOAc in methanol (8 mL) under nitrogen atmosphere at ambient temperature. After stirring at that temperature for 1 hour, a solution of sodium cyanoborohydride (250 mg, 3.6 mmol) in methanol was added. The resulting reaction mixture was stirred at ambient temperature for 24 hours at which time TLC showed no starting aldehyde. 3N aqueous HCl was added in 5 mL portions until bubbling subsided; pH was adjusted to 8 with saturated aqueous NaHCO3 solution. The resulting mixture was extracted with EtOAc (3×25 mL), the combined organic solution was washed with brine (50 mL) and dried over MgSO4. The solution was concentrated in vacuo affording an amber oil. The crude product was further purified by flash chromatography (20%-30% EtOAc in hexanes) affording 342 mg (41%) of the pure titled compound as a clear oil. APCI-MS m/z 488.3 (MH+).

1. customThe resulting reaction mixture
2. stirringwas stirred at ambient temperature for 24 hours at which time TLC
3. customuntil bubbling
4. extractionThe resulting mixture was extracted with EtOAc (3×25 mL)
5. washthe combined organic solution was washed with brine (50 mL)
6. dry with materialdried over MgSO4
7. concentrationThe solution was concentrated in vacuo
8. customaffording an amber oil
9. customThe crude product was further purified by flash chromatography (20%-30% EtOAc in hexanes)