Allyl bromide → 17-allyl-7alpha-[(2S)-3,3-dimethyl-2-hydroxybutan-2-yl]-4,5alpha-epoxy-3-hydroxy-6-methoxy-6alpha,14alpha-ethanomorphinan
Reaction equation
[CH3:1][C@@:2]([OH:30])([C:26]([CH3:29])([CH3:28])[CH3:27])[C@@H:3]1[C@@:8]2([O:24][CH3:25])[C@@H:9]3[O:23][C:18]4=[C:19]([OH:22])[CH:20]=[CH:21][C:16]5=[C:17]4[C@:10]43[CH2:11][CH2:12][NH:13][C@H:14]([CH2:15]5)[C@@:5]4(CC2)[CH2:4]1.C([O-])(O)=O.[Na+].[CH2:36](Br)[CH:37]=[CH2:38].[NH4+].[OH-].[CH3:42][C:43](N(C)C)=O>O>[CH2:36]([N:13]1[CH2:12][CH2:11][C@@:10]23[C:17]4[C:16]5[CH2:15][C@@H:14]1[C@H:5]2[CH2:4][C@H:3]([C@:2]([OH:30])([C:26]([CH3:27])([CH3:28])[CH3:29])[CH3:1])[C@H:8]([O:24][CH3:25])[C@@H:9]3[O:23][C:18]=4[C:19]([OH:22])=[C:20]1[CH2:43][CH2:42][C:21]1=5)[CH:37]=[CH2:38]Participants
7
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
To a mixture of norbuprenorphine (14) (5.6 g, 13.5 mMol) and NaHCO3 (3.4 g, 40.6 mMol) in DMAc (60 ml) was added dropwise at ambient temperature allyl bromide (1.4 ml, 16.3 mMol). The progress of the N-allylation was monitored by HPLC. After 5 h stirring at 60° C., the reaction was complete. The reaction mixture was added into water (100 ml). The pH of the resultant white suspension was adjusted to 9.0 with aqueous NH4OH (5 ml, 29 wt %). After aging at ambient temperature for 2 h, the suspension was filtered. The wet cake was washed with water (2×10 ml), dried in an oven at 50° C. under vacuum with N2-bleed to afford 5.97 g of compound 15 (Marton, J., et al., supra) (97.2% yield) as an off-white solid with a purity of 96.5%.
Workup
- waitAfter aging at ambient temperature for 2 h
- filtrationthe suspension was filtered
- washThe wet cake was washed with water (2×10 ml)
- dry with materialdried in an oven at 50° C. under vacuum with N2-
Sources & evidence
- ORD record
- ord-a3dbbfe07c8b4a1b9af1d82cdb7015df
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09315514B2
Reaction notes
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