Diisobutylaluminum hydride → 1(RS)-[1-(3,4-dichlorobenzyl)piperidin-4-ylmethyl]-2-methylpropanol

HRID 1840754Notes

Reaction equation

HRID 1840754 reaction equation
[CH3:1][CH:2](C[AlH]CC(C)C)[CH3:3].[Cl:10][C:11]1[CH:12]=[C:13]([CH:27]=[CH:28][C:29]=1[Cl:30])[CH2:14][N:15]1[CH2:20][CH2:19][CH:18]([CH2:21][C:22]([O:24]CC)=O)[CH2:17][CH2:16]1>C1(C)C=CC=CC=1>[Cl:10][C:11]1[CH:12]=[C:13]([CH:27]=[CH:28][C:29]=1[Cl:30])[CH2:14][N:15]1[CH2:16][CH2:17][CH:18]([CH2:21][CH:22]([OH:24])[CH:2]([CH3:3])[CH3:1])[CH2:19][CH2:20]1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 10758769Ethyl [1-(3,4-dichlorobenzyl)piperidin-4-yl]acetate

Product 1

HCID 222576701(RS)-[1-(3,4-dichlorobenzyl)piperidin-4-ylmethyl]-2-methylpropanolYield 39.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

DIBAL-H (6.9 ml, 10.35 mmol, 1.5 M in toluene) was added to a solution of ethyl [1-(3,4-dichlorobenzyl)piperidin-4-yl]acetate (1.9 g, 5.8 mmol) in dry toluene (60 ml) at −60° C. under nitrogen atmosphere. The reaction mixture was stirred at dry ice bath temperature for 0.5 h, quenched with saturated sodium bisulfite solution and then allowed to warm to room temperature. The aqueous layer was separated and basified with 2N sodium hydroxide to pH between 8-9 and the product was extracted with diethyl ether. The combined ether layers were washed with brine and dried over sodium sulfate. After concentration, the residue was dissolved in dry tetrahydrofuran (30 ml) and cooled to 0° C. Isopropyl magnesium chloride (2.0 M, 5.8 ml) was added dropwise and the resulting reaction mixture was allowed to warm to room temperature. After 0.5 h, the reaction mixture was quenched with water and extracted with diethyl ether. The ether layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified on silica gel column with 25% acetone, 25% dichloromethane in hexanes to give 1(RS)-[1-(3,4-dichlorobenzyl)piperidin-4-ylmethyl]-2-methylpropanol (0.75 g) as an oil.

Workup

  1. customquenched with saturated sodium bisulfite solution
  2. customThe aqueous layer was separated
  3. extractionthe product was extracted with diethyl ether
  4. washThe combined ether layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationAfter concentration
  7. dissolutionthe residue was dissolved in dry tetrahydrofuran (30 ml)
  8. temperaturecooled to 0° C
  9. additionIsopropyl magnesium chloride (2.0 M, 5.8 ml) was added dropwise
  10. customthe resulting reaction mixture
  11. temperatureto warm to room temperature
  12. waitAfter 0.5 h
  13. customthe reaction mixture was quenched with water
  14. extractionextracted with diethyl ether
  15. washThe ether layer was washed with brine
  16. dry with materialdried over sodium sulfate
  17. concentrationconcentrated in vacuo
  18. customThe residue was purified on silica gel column with 25% acetone, 25% dichloromethane in hexanes

Sources & evidence

ORD record
ord-fb966dcc3d9e42ada8eb3c9633b949a0
Source dataset
uspto-grants-2004_01
Patent number
US06683074B1

Reaction notes

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