Methyl iodide → Ethyl 4-(4-(cyclohexylmethyl)-4-methoxypiperidin-1-yl)benzoate
Reaction equation
[CH:1]1([CH2:7][C:8]2([OH:25])[CH2:13][CH2:12][N:11]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:28]N(C)P(N(C)C)(N(C)C)=O.CI>C1COCC1.OS([O-])(=O)=O.[Na+]>[CH:1]1([CH2:7][C:8]2([O:25][CH3:28])[CH2:13][CH2:12][N:11]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 50 °C
Procedure
A solution of Example 1F (380 mg) in THF (5 mL) was treated with NaH (96 mg, 60% dispersion in mineral oil), heated to 50° C. for 2 hours, and treated with hexamethylphosphoramide (1 mL) followed by MeI (1 mL). The reaction mixture was refluxed overnight, cooled to 0° C., and diluted with saturated aqueous NaHSO4 solution (10 mL). The resulting two-phase mixture was separated, the aqueous phase was extracted twice with ether, and the combined organic layers washed with water and brine. After drying over MgSO4, the mixture was concentrated in vacuo and purified by silica gel chromatography eluting with 15% ethyl acetate in hexanes.
Workup
- temperatureThe reaction mixture was refluxed overnight
- temperaturecooled to 0° C.
- customThe resulting two-phase mixture was separated
- extractionthe aqueous phase was extracted twice with ether
- washthe combined organic layers washed with water and brine
- dry with materialAfter drying over MgSO4
- concentrationthe mixture was concentrated in vacuo
- custompurified by silica gel chromatography
- washeluting with 15% ethyl acetate in hexanes
Sources & evidence
- ORD record
- ord-7d7f6722ea8647de8788777455c9b1cc
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09156856B2
Reaction notes
Loading…