5-Bromoindole → 4-(1H-Indol-5-yl)-1-methylpiperidin-4-ol
Reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[H-].[K+].C([Li])(C)(C)C.[CH3:18][N:19]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1>C1COCC1.CCCCC.C(OCC)(=O)C>[NH:7]1[C:8]2[C:4](=[CH:3][C:2]([C:22]3([OH:25])[CH2:23][CH2:24][N:19]([CH3:18])[CH2:20][CH2:21]3)=[CH:10][CH:9]=2)[CH:5]=[CH:6]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- -78 °C
Procedure
To a solution of 5-bromo-1H-indole (5.0 g, 25.5 mmol) in THF at −10° C. under argon, was added a solution of potassium hydride (1.13 g, 28.1 mmol) in THF (7 mL). The reaction mixture was then cooled to −78° C., and t-butyllithium (52.5 mL of a 1.7 M solution in pentane, 89.3 mmol) was added slowly, via syringe. The mixture was stirred for 15 minutes, and 1-methyl-4-piperidone (6.75 mL, 54.8 mmol) was quickly added. After the mixture was stirred at −78 ° C. for one hour, the solution was warmed to −20° C. and poured into a mixture of a buffer solution (20 mL, pH 7.0) and ethyl acetate (30 mL). The organic layer was washed with brine (30 mL) and dried (Na2SO4). The product was purified by column chromatography over silica gel using 5% 2M ammonia in methanol in dichloromethane as the eluent to provide the title compound (1.95 g, 35%).
Workup
- stirringAfter the mixture was stirred at −78 ° C. for one hour
- temperaturethe solution was warmed to −20° C.
- washThe organic layer was washed with brine (30 mL)
- dry with materialdried (Na2SO4)
- customThe product was purified by column chromatography over silica gel using 5% 2M ammonia in methanol in dichloromethane as the eluent
Sources & evidence
- ORD record
- ord-a7f930618ae84f96917103b78d759cb8
- Source dataset
- uspto-grants-2003_05
- Patent number
- US06562809B1
Reaction notes
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