Allyl bromide → Naloxone
Reaction equation
[CH2:1](Br)[CH:2]=[CH2:3].CCN(CC)CC.C[N:13]1[C@@H:23]2[CH2:24][C:25]3[CH:30]=[CH:29][C:28]([OH:31])=[C:27]4[O:32][C@H:17]5[C:18]([CH:20]=[CH:21][C@:22]2([OH:33])[C@:16]5([C:26]=34)[CH2:15][CH2:14]1)=[O:19]>CN1C(=O)CCC1.O.ClCCl>[CH2:3]=[CH:2][CH2:1][N:13]1[C@@H:23]2[CH2:24][C:25]3[CH:30]=[CH:29][C:28]([OH:31])=[C:27]4[O:32][C@H:17]5[C:18]([CH2:20][CH2:21][C@:22]2([OH:33])[C@:16]5([C:26]=34)[CH2:15][CH2:14]1)=[O:19]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 70 °C
Procedure
Allyl bromide (56 mg; 0.463 mmol) and Et3N (45 μl; 0.327 mmol) were added to a suspension of noroxymorphone (Example 5, 100 mg; 0.348 mmol) in a mixture of NMP/H2O (10:1; 0.35 mL). The reaction vessel was purged with argon and the mixture was stirred at 70° C. for 2 h. At that time, additional Et3N (45 μl; 0.327 mmol) was added and the mixture was stirred for an additional 7.5 h at 70° C. The reaction mixture was then cooled to room temperature, diluted with dichloromethane (15 mL), and washed with saturated NaHCO3 (3×3 mL). The aqueous layer was re-extracted with dichloromethane (5 mL) and the combined organic layers were dried over MgSO4. Column chromatography of the residue (dichloromethane/methanol 4:1) afforded 96 mg (84%) of naloxone as a white solid mp: 181-182° C. (ethyl acetate), [lit. mp 173-175]xix [lit. 179.5° C. (toluene)]xx identical in all respects to the material described in the literature.xxi
Workup
- customThe reaction vessel was purged with argon
- stirringthe mixture was stirred for an additional 7.5 h at 70° C
- temperatureThe reaction mixture was then cooled to room temperature
- washwashed with saturated NaHCO3 (3×3 mL)
- extractionThe aqueous layer was re-extracted with dichloromethane (5 mL)
- dry with materialthe combined organic layers were dried over MgSO4
Sources & evidence
- ORD record
- ord-29adc877c2fa4e2e867f1204b482daa4
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09045497B1
Reaction notes
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