Sodium hydride → 2-Adamantyl 4-((2-methoxy-2-oxoethoxy)methyl)-4-phenylpiperidine-1-carboxylate
Reaction equation
[OH:1][CH2:2][C:3]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:8][CH2:7][N:6]([C:9]([O:11][CH:12]2[CH:19]3[CH2:20][CH:15]4[CH2:16][CH:17]([CH2:21][CH:13]2[CH2:14]4)[CH2:18]3)=[O:10])[CH2:5][CH2:4]1.[H-].[Na+].Br[CH2:31][C:32]([O:34][CH3:35])=[O:33]>CN(C=O)C.CCOCC>[CH3:35][O:34][C:32](=[O:33])[CH2:31][O:1][CH2:2][C:3]1([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:8][CH2:7][N:6]([C:9]([O:11][CH:12]2[CH:19]3[CH2:20][CH:15]4[CH2:16][CH:17]([CH2:21][CH:13]2[CH2:14]4)[CH2:18]3)=[O:10])[CH2:5][CH2:4]1Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
To a stirred solution of 2-adamantyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (230 mg, 0.62 mmol) in dry DMF (5 mL) was added 60% NaH in oil (60 mg, 2.5 mmol). The mixture was stirred at rt for 0.5 h and methyl bromoacetate (0.24 mL, 2.5 mmol) was added. The mixture was stirred at 50° C. in an oil bath for 4 h. The mixture was diluted with ether (90 mL), washed with water (3×20 mL), dried over MgSO4 and concentrated to leave an oil (358 mg). This material was purified by column chromatography on silica gel, eluted with an EtOAc in hexanes gradient, followed by prep HPLC to afford the title compound (20 mg, 7%) as an oil. LC-MS Method 2 tR=11.79 min, m/z=442.
Workup
- stirringThe mixture was stirred at 50° C. in an oil bath for 4 h
- washwashed with water (3×20 mL)
- dry with materialdried over MgSO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-87bea2927fb3439e8f5c3a5b152c25fd
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09163012B2
Reaction notes
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