Acetaldehyde → N-(2-(3-methoxyphenyl)ethyl)-4-(2-(1-hydroxyethyl)-5-methoxybenzyl)piperidine

HRID 1006064Notes

Reaction equation

HRID 1006064 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([CH2:17][C:18]3[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=3Br)[CH2:13][CH2:12]2)[CH:6]=[CH:7][CH:8]=1.C([Li])CCC.[CH:32](=[O:34])[CH3:33].C(=O)([O-])O.[Na+]>O1CCCC1.CCCCCC>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([CH2:17][C:18]3[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=3[CH:32]([OH:34])[CH3:33])[CH2:13][CH2:12]2)[CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 177AcetaldehydeHCID 516892Sodium BicarbonateHCID 22675297N-(2-(3-methoxyphenyl)ethyl)-4-(2-bromo-5-methoxybenzyl)piperidineHCID 178418339Butyllithium

Product 1

HCID 22675304N-(2-(3-methoxyphenyl)ethyl)-4-(2-(1-hydroxyethyl)-5-methoxybenzyl)piperidineYield 84%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

A solution of N-(2-(3-methoxyphenyl)ethyl)-4-(2-bromo-5-methoxybenzyl)piperidine (the compound of Example 64) (500 mg, 1.2 mmol) in tetrahydrofuran (5 ml) was cooled to −78° C., and n-butyllithium (a 1.57M hexane solution, 910 μl, 1.4 mmol) was added dropwise thereto. After the resulting solution was stirred at the same temperature for 30 minutes, acetaldehyde (135 μl, 2.4 mmol) was added dropwise thereto, and the reaction mixture was stirred at the same temperature for another 1 hour. A saturated aqueous sodium hydrogencarbonate solution was added thereto and the resulting mixture was slowly heated to room temperature. Then, the mixture was extracted with ethyl acetate and the combined extract layer was washed with a saturated aqueous sodium chloride solution. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by a silica gel column chromatography (chloroform/methanol=30/1 to 10/1) to obtain the title compound (386 mg, 84%) as a brown oil.

Workup

  1. stirringthe reaction mixture was stirred at the same temperature for another 1 hour
  2. extractionThen, the mixture was extracted with ethyl acetate
  3. extractionthe combined extract layer
  4. washwas washed with a saturated aqueous sodium chloride solution
  5. dry with materialAfter drying over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customthe residue was purified by a silica gel column chromatography (chloroform/methanol=30/1 to 10/1)

Sources & evidence

ORD record
ord-aa21d129feae4e59b1b6ad2c602f2484
Source dataset
uspto-grants-2004_09
Patent number
US06787560B2

Reaction notes

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