N-Methylmorphine → (4S)-3-[3-(5-methylindolyl)propanoyl]-4-phenyl-1,3-oxazolidin-2-one

HRID 498981Notes

Reaction equation

HRID 498981 reaction equation
[C:1]1([C@H:7]2[CH2:11][O:10][C:9](=[O:12])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]CCCC.[CH3:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23]([CH2:28][CH2:29][C:30](O)=[O:31])=[CH:22]2.CC(C)(C)C(Cl)=O.C[N+]1(C)[C@H]2CC3C=CC(O)=C4O[C@H]5[C@@H](O)C=C[C@@H]2[C@]5(C=34)CC1>C1COCC1>[CH3:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23]([CH2:28][CH2:29][C:30]([N:8]1[C@@H:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:11][O:10][C:9]1=[O:12])=[O:31])=[CH:22]2

Participants

7

Reactant 5

HCID 61063N-MethylmorphineHCID 62493Pivaloyl chlorideHCID 7304242-Oxazolidinone, 4-phenyl-, (4S)-HCID 684946453-(5-Methylindolyl)propanoic acidHCID 178418339Butyllithium

Product 1

HCID 68492500(4S)-3-[3-(5-methylindolyl)propanoyl]-4-phenyl-1,3-oxazolidin-2-oneYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To the suspension of (4S)-4-phenyl-1,3-oxazolidin-2-one (6.85 g, 42 mmol) in anhydrous THF (130 mL) was added BuLi (26.3 mL, 42 mmol) at −78° C. and the mixture was stirred under argon (0.5 h). To the above suspension was added a solution of active ester prepared by reacting 3-(5-methylindolyl)propanoic acid 7 (10.23 g, 50.39 mmol) in anhydrous THF (130 mL) and trimethylacetyl chloride (5.10 g, 50.39 mmol) in the presence of N-methyl morphine (6.06 g, 50.39 mmol) at 0° C. under argon, followed by stirring at −78° C. (1 h). The combined reaction mixture was stirred at −78° C. for an additional 2 h, then the solution was warmed to room temperature and stirred overnight. The reaction was quenched by the addition of ice-cold saturated NH4Cl solution (120 mL), extracted with EtOAc, washed with brine and dried (Na2SO4). Evaporation provided a residue, which was purified by silica gel flash chromatography to provide 8 as colorless oil. (12.7 g, 87% yield). 1H NMR (d6-DMSO) δ 7.36-7.23 (m, 8H), 6.94 (dd, 1H, J=1.5 Hz & 8.5 Hz), 6.28 (dd, 1H, J=0.8 Hz & 3.1 Hz), 5.43: (dd, 1H, J=3.5 Hz & 8.6 Hz), 4.70 (t, 1H, J=8.8), 4.40 (s, 1H), 4.40-4.37 (m, 2H), 4.15 (dd, 1H, J=3.5 Hz & 8.8 Hz), 3.41-3.30 (m, 2H), 2.36 (s, 3H). FABMS (+Ve) m/z 348 [M+], 349 [MH+]. Anal. Calcd for C21H20N2O3 C, 72.40; H, 5.79; N, 8.04. Found C, 72.33; H, 5.77; N, 8.15.

Workup

  1. customprepared
  2. customat 0° C.
  3. stirringby stirring at −78° C. (1 h)
  4. customThe combined reaction mixture
  5. stirringwas stirred at −78° C. for an additional 2 h
  6. stirringstirred overnight
  7. customThe reaction was quenched by the addition of ice-cold saturated NH4Cl solution (120 mL)
  8. extractionextracted with EtOAc
  9. washwashed with brine
  10. dry with materialdried (Na2SO4)
  11. customEvaporation
  12. customprovided a residue, which
  13. customwas purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-89ab729a031c4666b5947a89aa186539
Source dataset
uspto-grants-2010_08
Patent number
US07767645B2

Reaction notes

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