Bromomethylcyclopropane → HCID 57147379、化合物
反応式
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH2:7][C@H:8]3[NH:19][CH2:18][CH2:17][C@@:14]4([C:15]=2[CH:16]=1)[C@@:9]3([O:21][CH3:22])[CH2:10][CH2:11][C:12](=[O:20])[CH2:13]4.[CH:23]1([CH2:26]Br)[CH2:25][CH2:24]1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH:23]1([CH2:26][N:19]2[CH2:18][CH2:17][C@@:14]34[C:15]5[CH:16]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=5[CH2:7][C@@H:8]2[C@:9]3([O:21][CH3:22])[CH2:10][CH2:11][C:12](=[O:20])[CH2:13]4)[CH2:25][CH2:24]1参加物
5
反応条件
- 温度
- 110 °C
実験手順
A mixture of 3,14-dimethoxymorphinan-6-one (6a) (4.491 g, 14.9 mmol), cyclopropylmethyl bromide (3.017 g, 22.35 mmol) and NaHCO3 (7.50 g, 89.4 mmol) in DMF (50 ml) was refluxed under nitrogen for 16 hours at 110° C. The mixture was filtered and the DMF removed by distillation under reduced pressure. The residue was taken up in methylene chloride (150 ml) and 150 ml of water. The two layers were separated and the aqueous layer re-extracted with methylene chloride (2×100 ml). The organic solutions were combined, washed with water (100 ml), dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting yellow solid was chromatographed on Florisil using graded methanol/chloroform as the eluant to give 17-cyclopropylmethyl-3,14-dimethoxymorphinan-6-one as a yellow oil which crystallized after drying the give 4.132 g (78% theory) of yellow solid. Recrystallization from ethanol gave 3.443 g (65%) of the title compound (8) (TR-5400) as colorless needles. A portion of 8 was converted to the hydrochloride salt (TR-5305) by treatment with ethereal hydrogen chloride to give a white solid, m.p. 215°-128° C.