Water → 1-Benzyl-4-(2-chloroquinolin-3-yl)piperidin-4-ol
Reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C([N-]C(C)C)(C)C.[Li+].[CH2:20]([N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][C:28]1=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[OH2:34]>C1COCC1>[CH2:20]([N:27]1[CH2:32][CH2:31][C:30]([C:11]2[C:2]([Cl:1])=[N:3][C:4]3[C:9]([CH:10]=2)=[CH:8][CH:7]=[CH:6][CH:5]=3)([OH:34])[CH2:29][CH2:28]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
Under an argon atmosphere 22.3 g (136 mmol) 2-chloroquinoline in 60 mL THF was slowly added dropwise at −78° C. to 68.0 mL (136 mmol) of a 2M lithium diisopropylamide (in THF) solution in 280 mL THF. The reaction mixture was stirred for 1 h at −78° C. and then 24.3 mL (136 mmol) N-benzylpiperidone in 50 mL of THF were added dropwise. The reaction mixture was stirred for 40 min at −70° C. and for 3 h at RT. The reaction mixture was cooled to −20° C., and 200 mL water were added dropwise. The reaction mixture was allowed to come up to RT and extracted with EtOAc. The organic phase was dried, filtered and concentrated to dryness by rotary evaporation. The product was purified using an Alox column. The product-containing fractions were combined and concentrated to dryness by rotary evaporation.
Workup
- stirringThe reaction mixture was stirred for 40 min at −70° C. and for 3 h at RT
- temperatureThe reaction mixture was cooled to −20° C.
- customto come up to RT
- extractionextracted with EtOAc
- customThe organic phase was dried
- filtrationfiltered
- concentrationconcentrated to dryness by rotary evaporation
- customThe product was purified
- concentrationconcentrated to dryness by rotary evaporation
Sources & evidence
- ORD record
- ord-7ad3bc61e8654529b20e12021a07e38b
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08829006B2
Reaction notes
Loading…