Tert-butyl 8-(2,2-difluoroethyl)-10-[methoxy(methyl)carbamoyl]-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate → Tert-butyl 8-(2,2-difluoroethyl)-10-propanoyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Participants

Reaction Steps

To tert-butyl 8-(2,2-difluoroethyl)-10-[methoxy(methyl)carbamoyl]-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (295 mg, 0.72 mmol) in THF (3 mL) at −78° C. under an atmosphere of nitrogen, was added ethylmagnesium bromide (1.7 mL of 1 M in THF, 1.7 mmol) dropwise. The reaction mixture was stirred at the same temperature for 0.5 hours, then at 0° C. for 1 hour. The reaction mixture was quenched with ethyl acetate (20 mL) and sat. aq. NaHCO3 (10 mL). The aqueous layer was further extracted with EtOAc (2×20 mL), and the combined organics were dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel column chromatography (0-100% ethyl acetate/hexane) to give tert-butyl 8-(2,2-difluoroethyl)-10-propanoyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (227 mg, 83%) as a colorless oil. ESI-MS m/z calc. 376.2. found 377.3 (M+1)+; Retention time: 1.76 minutes. 1H NMR (400 MHz, CDCl3) δ 6.01-5.70 (m, 1H), 4.21-4.15 (m, 1H), 3.91-3.75 (m, 2H), 3.33-3.22 (m, 1H), 3.15-2.98 (m, 2H), 2.79-2.57 (m, 5H), 2.43-2.35 (m, 1H), 2.19-2.06 (m, 2H), 1.61-1.39 (m, 12H), 1.06 (t, J=7.3 Hz, 3H).

Provenance & Evidence