Proton sponge → Norcodeine hydrochloride

HRID 613679ノート

反応式

HRID 613679 の反応式
CC([O:4][C@@H:5]1[C@@H:14]2[O:15][C:16]3=[C:17]([O:20][CH3:21])[CH:18]=[CH:19][C:11]4=[C:12]3[C@:13]32[CH2:22][CH2:23][N:24](C)[C@H:9]([CH2:10]4)[C@@H:8]3[CH:7]=[CH:6]1)=O.[Cl:26]C(OC(Cl)C)=O.CN(C1C2C(N(C)C)=CC=CC=2C=CC=1)C>C(Cl)Cl>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:11]2[CH2:10][C@H:9]3[NH:24][CH2:23][CH2:22][C@:13]45[C@H:14]([C@@H:5]([OH:4])[CH:6]=[CH:7][C@@H:8]34)[O:15][C:16]=1[C:12]=25.[ClH:26]

参加物

5

反応物 3

HCID 88675Proton spongeHCID 5213051-Chloroethyl chloroformateHCID 5486550Acetylcodeine

生成物 1

HCID 60196311Norcodeine hydrochloride収率 93.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A solution of 6-acetylcodeine (10.0 g, 29.3 mmol), 1-chloroethyl chloroformate (5.56 g,38.1 mmol), and proton sponge (1.0 g) in methylene chloride (50 ml) was heated at reflux for 50 min. The reaction mixture was evaporated in vacuo to about 30 ml. Methanol (25 ml) and concentrated HCl (2 ml) were added. The solution was heated at reflux for 40 min. and evaporated in vacuo to almost dryness. The residue was added hexane and filtered to give norcodeine hydrochloride (8.8 g, 93% yield). IR (KBr), (ν, cm-1): 3540 (NH), 3380 (6--OH), 2800-2600 (broad) and 2480 (sharp) (NH·HCl); NMR (δH)(DMSO-d6): 9.66 (2, s (broad), 17--N+H2Cl-), 6.72 (1, d, J, 8.2, 2-H), 6.57 (1, d, J, 8.2, 1-H), 5.66 (1, dt, J, 9.9 & 3.0, 7-H), 5.28 (1, dt, J, 9.8 & 3.0, 8-H), 5.10 (1, s (broad), 6--OH), 4.82 (1, dd, J, 6.1 & 1.2, 5-H), 4.15 (2, m, 6-H & 9-H), 3.77 (3, s, 3--OCH3), 3.22 (1, d, J, 19.1, 10-Hβ), 3.21 (1, td, J, 13.2 & 4.1, 16-He), 3.06 (1, m, 14-H), 2.91 (1, dd, J, 18.5 & 6.3, 10-Hα), 2.79 (1, dd, J, 13.0 & 3.9, 16-Ha), 2.22 (1, td, J, 13.4 & 4.9, 15-Ha) and 1.89 (1, dd, J, 13.6 & 2.7, 15-He).

後処理

  1. temperatureat reflux for 50 min
  2. customThe reaction mixture was evaporated in vacuo to about 30 ml
  3. additionMethanol (25 ml) and concentrated HCl (2 ml) were added
  4. temperatureThe solution was heated
  5. temperatureat reflux for 40 min.
  6. customevaporated in vacuo to almost dryness
  7. additionThe residue was added hexane
  8. filtrationfiltered

出典と根拠

ORDレコード
ord-e3eabd48016440ab8056aad0f05e68f7
出典データセット
uspto-grants-1999_12
特許番号
US06008355

反応ノート

読み込み中…