Chloromethyl methyl sulfide → (+)[N-(Benzyloxycarbonyl)morphinan-3-yloxy]methyl methyl sulfide
Reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[CH:6][C:7]2[CH2:8][C@H:9]3[N:20]([C:21]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[O:22])[CH2:19][CH2:18][C@@:15]4([C:16]=2[CH:17]=1)[C@H:10]3[CH2:11][CH2:12][CH2:13][CH2:14]4.[CH3:31][S:32][CH2:33]Cl>CN(P(N(C)C)(N(C)C)=O)C>[CH3:31][S:32][CH2:33][O:3][C:4]1[CH:5]=[CH:6][C:7]2[CH2:8][C@H:9]3[N:20]([C:21]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[O:22])[CH2:19][CH2:18][C@@:15]4([C:16]=2[CH:17]=1)[C@H:10]3[CH2:11][CH2:12][CH2:13][CH2:14]4Participants
5
Procedure
To Sodium hydride (763 mg of 60% dispersion in mineral oil, 19.1 mmol) in HMPA (15 mL) was added a solution of (+)-3-hydroxy-N-(benzyloxycarbonyl)morphinan (6.00 g, 15.9 mmol) from Example 1 in HMPA (50 mL) at room temperature. The reaction mixture was stirred for 30 min and then chloromethyl methyl sulfide (1.60 mL, 19.1 mmol) was added dropwise. The reaction mixture was stirred vigorously at room temperature overnight. The product was extracted with EtOAc (500 mL). The EtOAc layer was washed with saturated NaHCO3 solution and dried over MgSO4, filtered and evaporated under vacuum to provide the crude product, which was further purified by prep reverse-phase HPLC to afford the title compound (1.78 g, 26%) as a yellow gum.
Workup
- stirringThe reaction mixture was stirred vigorously at room temperature overnight
- extractionThe product was extracted with EtOAc (500 mL)
- washThe EtOAc layer was washed with saturated NaHCO3 solution
- dry with materialdried over MgSO4
- filtrationfiltered
- customevaporated under vacuum
- customto provide the crude product, which
- customwas further purified by prep reverse-phase HPLC
Sources & evidence
- ORD record
- ord-50b87131f6e64864906f12ea4d863030
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08178551B2
Reaction notes
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