Acetic Anhydride → 1-[(4R,4aR,7S,7aR,12bS)-7,9-dihydroxy-3-methyl-1,2,4,4a,7,7a,10,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl]ethanone

HRID 613666Notes

Reaction equation

HRID 613666 reaction equation
[CH:1]1[C:17]2[CH2:16][C@H:15]3[N:18]([CH2:20][CH2:21][C@@:7]45[C@H:14]3[CH:13]=[CH:12][C@H:10]([OH:11])[C@@H:8]4[O:9][C:5]([C:6]=25)=[C:3]([OH:4])[CH:2]=1)[CH3:19].C([O-])(O)=O.[Na+].[CH3:27][C:28](OC(C)=O)=[O:29]>C1(C)C=CC=CC=1.CC#N>[C:28]([C:3]1([OH:4])[C:5]2[O:9][C@@H:8]3[C@@:7]45[CH2:21][CH2:20][N:18]([CH3:19])[C@@H:15]([C@@H:14]4[CH:13]=[CH:12][C@@H:10]3[OH:11])[CH2:16][C:17]([C:6]5=2)=[CH:1][CH2:2]1)(=[O:29])[CH3:27]

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 5288826Morphine

Product 1

HCID 222119501-[(4R,4aR,7S,7aR,12bS)-7,9-dihydroxy-3-methyl-1,2,4,4a,7,7a,10,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl]ethanoneYield 100%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of morphine (23.63 g, 83 mmol), NaHCO3 (28.2 g, 336 mmol), Ac2O (8.69 g, 85 mmol) in toluene (500 ml) and CH3CN (900 ml) was heated at reflux for 21 hrs. The reaction mixture was evaporated to dryness in vacuo. To the residue was added water (80 ml) and extracted with chloroform (500 ml). The extracts were dried, combined and evaporated to dryness in vacuo to obtain a residue, which was chromatographed on silica gel (column: d=6 cm, I=8 cm, packed with 141 g of silica gel; solvent system: 5-10% MeOH in CH2Cl2) to yield 3-acetylmorphine (27 g, 100% yield). IR (KBr)(ν, cm-1): 3500 (m, sharp, --OH), 1750 (s, sharp, AcO); NMR (δH)(CDCl3): 6.73(1, d, J, 8.1,2-H), 6.57(1, d, J, 8.1, 1-H), 5.74(1, dm, J, 10.1,7-H), 5.25 (1, dm, J, 9.9, 8-H), 4.91 (1, d, J, 6.9, 5-H), 4.25-4.10 (1, m, 6-H), 3.50-3.35 (1, m, 9-H), 3.05(1, d, J, 19.1, 10-Hβ), 2.8-2.7 (1, m, 14-H), 2.85-2.60 (1, m, 16-He), 2.50-2.25 (1, m, 16-Ha), 2.45 (3, s, NCH3), 2.5-2.2 (1, m, 10-Hα), 2.28 (3, s, AcO), 2.06 (1, td, J, 12.1 & 5.0, 15-Ha), 2.0-1.85 (1, m, 15-He).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 21 hrs
  3. customThe reaction mixture was evaporated to dryness in vacuo
  4. additionTo the residue was added water (80 ml)
  5. extractionextracted with chloroform (500 ml)
  6. customThe extracts were dried
  7. customevaporated to dryness in vacuo
  8. customto obtain a residue, which
  9. customwas chromatographed on silica gel (column: d=6 cm, I=8 cm, packed with 141 g of silica gel; solvent system: 5-10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-0b34cb4909de4f4db20c79692a02dba4
Source dataset
uspto-grants-1999_12
Patent number
US06008354

Reaction notes

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