Cesium carbonate → (+)[N-(Benzyloxycarbonyl)morphinan-3-yloxy]methyl isopropyl carbonate

HRID 1924435Notes

Reaction equation

HRID 1924435 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:6][C@H:7]3[N:18]([C:19]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[O:20])[CH2:17][CH2:16][C@@:13]4([C:14]=2[CH:15]=1)[C@H:8]3[CH2:9][CH2:10][CH2:11][CH2:12]4.C(=O)([O-])[O-].[Cs+].[Cs+].[C:35](=[O:43])([O:39][CH:40]([CH3:42])[CH3:41])[O:36][CH2:37]I>CC(C)=O>[C:35](=[O:43])([O:39][CH:40]([CH3:42])[CH3:41])[O:36][CH2:37][O:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:6][C@H:7]3[N:18]([C:19]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[O:20])[CH2:17][CH2:16][C@@:13]4([C:14]=2[CH:15]=1)[C@H:8]3[CH2:9][CH2:10][CH2:11][CH2:12]4

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 15870216Iodomethyl propan-2-yl carbonate2×HCID 538511903-hydroxy-N-(benzyloxycarbonyl)morphinan

Product 1

HCID 67519177(+)[N-(Benzyloxycarbonyl)morphinan-3-yloxy]methyl isopropyl carbonateYield 97.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To (+)-3-hydroxy-N-(benzyloxycarbonyl)morphinan (33.0 g, 87.4 mmol) and cesium carbonate (28.5 g, 87.4 mmol) in acetone (450 mL) was added iodomethyl isopropyl carbonate (21.3 g, 87.4 mmol) (see Rigel Pharmaceuticals, Inc. US2006/247287 A1, Appl.; US2006-381215 (2006 May 2)) at room temperature. The reaction mixture was stirred vigorously at room temperature overnight. The acetone was then removed by rotary evaporation under vacuum. To the residue was added saturated NaHCO3 solution. The mixture was extracted with EtOAc (300 mL×2). The combined organics were washed with 1N HCl solution (300 mL), dried over MgSO4, filtered, and evaporated under vacuum to provide the title compound (42.0 g, 97%) as a yellow gum.

Workup

  1. customThe acetone was then removed by rotary evaporation under vacuum
  2. additionTo the residue was added saturated NaHCO3 solution
  3. extractionThe mixture was extracted with EtOAc (300 mL×2)
  4. washThe combined organics were washed with 1N HCl solution (300 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated under vacuum

Sources & evidence

ORD record
ord-c08443d89ddb4993a5abc08c75d52435
Source dataset
uspto-grants-2012_05
Patent number
US08178551B2

Reaction notes

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