Acetic Anhydride → 6-Acetylcodeine

HRID 613670Notes

Reaction equation

HRID 613670 reaction equation
[CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:21][CH3:22])=[C:11]4[O:12][C@H:13]5[C@@H:14]([OH:20])[CH:15]=[CH:16][C@@H:17]2[C@:5]5([C:6]=34)[CH2:4][CH2:3]1.[C:23](OC(=O)C)(=[O:25])[CH3:24].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[CH3:24][C:23]([O:20][C@@H:14]1[C@@H:13]2[O:12][C:11]3=[C:10]([O:21][CH3:22])[CH:9]=[CH:8][C:7]4=[C:6]3[C@:5]32[CH2:4][CH2:3][N:2]([CH3:1])[C@H:18]([CH2:19]4)[C@@H:17]3[CH:16]=[CH:15]1)=[O:25]

Participants

7

Reactant 4

HCID 7918Acetic Anhydride2×HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5284371Codeine

Product 1

HCID 54865506-AcetylcodeineYield 99.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of codeine (30 g, 100.2 mmol), acetic anhydride (18.4 g, 180.2 mmol), triethylamine (18.25 g, 180.2 mmol) and 4-dimethylaminopyridine (0.5 g) in dry ethyl acetate (620 ml) was stirred at rt. under nitrogen for 12 hr, added saturated aqueous sodium bicarbonate solution until no acetic anhydride detected. The organic portion was separated, washed with water (3×120 ml), dried over anhydrous sodium sulfate, and evaporated in vacuo to dryness to give 6-acetylcodeine as white solids (34.0 g, 99% yield). IR (KBr)(ν, cm-1): 1725 (st, sharp, 3-AcO); NMR (δH)(CDCl3): 6.66 (1, d, J, 8.2, 2-H), 6.53 (1, d, J,8.2, 1-H), 5.63 (1, ddd, J, 10.0, 2.4 & 1.0, 7-H), 5.42 (1, dt, J, 9.9 & 2.3, 8-H), 5.22-5.51 (1, m, 6-H), 5.06 (dd, J, 6.7 & 1.0, 5-H), 3.85 (3, s, 3-OCH3), 3.39 (1, dd, J, 6.0 & 3.3, 9-H), 3.03 (1, d, Jjem, 18.6, 10-Hβ), 2.78 (1, dd, J, 5.2 & 2.6, 14-H), 2.63 (1, dd, J, 11.9 & 4.6, 16-Ha), 2.45 (3, s, N-CH3), 2.40 (1, td, J, 12.0 & 3.8, 16-He), 2.33 (1, dd, J, 18.5 & 6.0, 10-Hα), 2.15 (3, s, 6-OAc), 2.06 (1, td, J, 12.0 & 5.0, 15-Ha) and 1.85 (1, dm, J, 12.0, 15-He).

Workup

  1. customThe organic portion was separated
  2. washwashed with water (3×120 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customevaporated in vacuo to dryness

Sources & evidence

ORD record
ord-3cbe514e06d144f2b44dac4b721fb8e3
Source dataset
uspto-grants-1999_12
Patent number
US06008354

Reaction notes

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