Proton sponge → Norcodeine hydrochloride

HRID 582267ノート

反応式

HRID 582267 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), (v, 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-d8cdd9017d1844d386c33574a3967781
出典データセット
uspto-grants-1999_07
特許番号
US05922876

反応ノート

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