Sulfuryl chloride → (+)-[N-(benzyloxycarbonyl)morphinan-3-yloxy]methyl chloride
Reaction equation
CS[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]2[CH2:9][C@H:10]3[N:21]([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])[CH2:20][CH2:19][C@@:16]4([C:17]=2[CH:18]=1)[C@H:11]3[CH2:12][CH2:13][CH2:14][CH2:15]4.S(Cl)([Cl:35])(=O)=O>C(Cl)Cl>[CH2:25]([O:24][C:22]([N:21]1[CH2:20][CH2:19][C@@:16]23[C:17]4[CH:18]=[C:5]([O:4][CH2:3][Cl:35])[CH:6]=[CH:7][C:8]=4[CH2:9][C@@H:10]1[C@@H:11]2[CH2:12][CH2:13][CH2:14][CH2:15]3)=[O:23])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1Participants
4
Procedure
To (+)[N-(Benzyloxycarbonyl)morphinan-3-yloxy]methyl methyl sulfide (1.78 g, 4.07 mmol) in DCM (40 mL) was added sulfuryl chloride (6.1 mL, 6.11 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight. After removal of excess reagent and DCM by rotary evaporation, the product was dried under vacuum to afford (+)-[N-(benzyloxycarbonyl)morphinan-3-yloxy]methyl chloride as a yellow gum. Then, it was added to a stirred suspension of cesium carbonate (1.59 g, 4.88 mmol) and isobutyric acid (0.45 mL, 4.88 mmol) in acetone (20 mL) at room temperature. The reaction mixture was stirred at room temperature overnight. After the reaction was completed, the reaction mixture was filtered and evaporated under vacuum to provide the crude product, which was further purified by prep reverse-phase HPLC to afford the title compound (0.844 g, 43%) as a yellow solid.