反应详情

To a colorless solution of 7-(hydroxymethyl)-7-methyl-3-neopentyl-1-oxa-3-azaspiro[4.5]decan-2-one (14.7 g, 54.6 mmol) in MeCN (273 ml) was added dibromotriphenylphosphorane (34.6 g, 82.0 mmol). The reaction was stirred at rt for 3 h and then heated to 80° C. for 42 h. The reaction was cooled to rt and concentrated onto florisil for purification on a 220 g silica gel column (5-15% EtOAc/hexanes, 30 min gradient; 15% EtOAc/hexanes, 10 min; 15-50% EtOAc/hexanes, 15 min gradient; 50% EtOAc/hexanes, 15 min; 50-100% EtOAc/hexanes, 5 min gradient; 100% EtOAc, 5 min; 100 mL/min elution; 254 nm detection) to yield the title compound (9.7 g, 54% yield). 1H NMR (400 MHz, CDCl3) δ 3.35 (dd, J=8.78, 12.05 Hz, 2H), 3.26 (s, 2H), 3.08 (d, J=14.05 Hz, 1H), 2.93 (d, J=14.05 Hz, 1H), 1.96-2.03 (m, 1H), 1.78 (dt, J=1.95, 14.18 Hz, 1H), 1.52-1.65 (m, 3H), 1.28-1.48 (m, 3H), 1.24 (s, 3H), 0.97 (s, 9H).

1. temperatureheated to 80° C. for 42 h
2. temperatureThe reaction was cooled to rt
3. concentrationconcentrated onto florisil for purification on a 220 g silica gel column (5-15% EtOAc/hexanes, 30 min gradient; 15% EtOAc/hexanes, 10 min; 15-50% EtOAc/hexanes, 15 min gradient; 50% EtOAc/hexanes, 15 min; 50-100% EtOAc/hexanes, 5 min gradient; 100% EtOAc, 5 min; 100 mL/min elution; 254 nm detection)