Proton sponge → N-Norcodeine hydrochloride

HRID 613671Notes

Reaction equation

HRID 613671 reaction equation
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]

Participants

5

Reactant 3

HCID 88675Proton spongeHCID 5213051-Chloroethyl chloroformateHCID 54865506-Acetylcodeine

Product 1

HCID 60196311N-Norcodeine hydrochlorideYield 93.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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 & 9.7) 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).

Workup

  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

Sources & evidence

ORD record
ord-3859a0b54b894d14b4209b2b6685253e
Source dataset
uspto-grants-1999_12
Patent number
US06008354

Reaction notes

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