Chloroacetyl chloride → HCID 16639031、化合物

反応式

[Cl:1][CH2:2][C:3](Cl)=[O:4].C(N(CC)CC)C.[CH3:13][O:14][C:15]1[CH:32]=[CH:31][C:18]2[CH2:19][NH:20][CH2:21][CH2:22][C@@:23]34[C@@H:28]([O:29][C:16]=1[C:17]=23)[CH2:27][C@@H:26]([OH:30])[CH:25]=[CH:24]4>>[Cl:1][CH2:2][C:3]([N:20]1[CH2:21][CH2:22][C:23]23[CH:24]=[CH:25][C@H:26]([OH:30])[CH2:27][CH:28]2[O:29][C:16]2=[C:15]([O:14][CH3:13])[CH:32]=[CH:31][C:18](=[C:17]32)[CH2:19]1)=[O:4]

参加物

反応物 3

HCID 6577Chloroacetyl chloride

HCID 8471Triethylamine

HCID 9838394N-Desmethylgalantamine

生成物 1

HCID 16639031HCID 16639031、化合物収率 7.7%

実験手順

0.82 g of chloroacetyl chloride (7.3 mmol) and 0.81 g (8.0 mmol) of triethylamine were added to a solution of (+/−)-norgalanthamine (2.0 g, 7.3 mmol) in dry TRF (100 ml). The reaction mixture was refluxed for 3 hours and concentrated by evaporation. The residue was diluted with 2N hydrochloric acid (100 ml) and extracted with EtOAc (3×75 ml). The aqueous phase was set at pH>8.5 with concentrated ammonia and extracted with 3×75 ml of CH2Cl2. The combined, organic phases were washed with common salt solution, dried on sodium sulfate and concentrated by evaporation. Flash chromatography yielded 0.20 g (7.7% of compound 4j): 1H-NMR (CDCl3) δ 6.78 (b, 1H), 6.12 (m, 2H), 5.30 (d, J=11.0 Hz, 1H), 4.65 (m, 2H), 4.32–4.01 (m, 3H), 3.78 (s, 3H), 3.59 (m, 1H), 3.06 (m, 1H), 2.61 (d, J=16.0 Hz, 1H), 1.90 (m, 3H), 13C-NMR (CDCl3) δ 166.0 (s) 146.2 (s), 144.9 (s), 132.3 (d), 128.3 (s), 127.3 (s), 126.0 (d), 120.2 (d), 111.2 (d), 88.2 (d), 61.7 (d), 55.8 (q), 52.8 (t), 48.1 (s), 45.5 (t), 41.4 (t), 35.4 (t), 29.6 (t).