反应详情

1,1-Dimethylethyl 4-oxo-1-piperidinecarboxylate (38.9 g, 195 mmol) and 1-(2-fluoroethyl)piperazine dihydrochloride (20 g, 97 mmol) were dissolved in 485 mL 1,2-DCE. TEA (81.5 mL, 585 mmol) was added and the reaction was stirred for 30 min. HOAc (8.4 mL, 146 mmol) was added and the reaction was stirred for an additional 30 min followed by the addition of sodium triacetoxyborohydride (49.6 g, 234 mmol). The reaction was stirred overnight. Saturated aqueous NaHCO3 solution was added carefully until the reaction stopped bubbling. Aqueous layer was then extracted with DCM (1×) and EtOAc (3×). Combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The resulting crude product was absorbed onto silica gel and purified by flash chromatography to give title compound of step C (28.95 g, 94%). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.39-4.57 (m, 2H), 3.90 (d, J=12.46 Hz, 2H), 2.61-2.73 (m, 2H), 2.47-2.61 (m, 2H), 2.36-2.47 (m, 8H), 2.24-2.35 (m, 1H), 1.69 (d, J=12.46 Hz, 2H), 1.37 (s, 9H), 1.14-1.26 (m, 2H).

1. stirringthe reaction was stirred for an additional 30 min
2. stirringThe reaction was stirred overnight
3. customstopped bubbling
4. extractionAqueous layer was then extracted with DCM (1×) and EtOAc (3×)
5. dry with materialCombined organic layers were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe resulting crude product was absorbed onto silica gel
9. custompurified by flash chromatography