Citric Acid → 4-[2-(5-Bromo-2-chloropyridin-4-yl)-1-hydroxy-ethyl]piperidine-1-carboxylic acid tert-butyl ester

HRID 1622232Notes

Reaction equation

HRID 1622232 reaction equation
[BH4-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([C:16](=[O:26])[CH2:17][C:18]2[C:23]([Br:24])=[CH:22][N:21]=[C:20]([Cl:25])[CH:19]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.O>[C:3]([O:7][C:8]([N:10]1[CH2:11][CH2:12][CH:13]([CH:16]([OH:26])[CH2:17][C:18]2[C:23]([Br:24])=[CH:22][N:21]=[C:20]([Cl:25])[CH:19]=2)[CH2:14][CH2:15]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 311Citric AcidHCID 4311764Sodium borohydrideHCID 866748944-[2-(5-Bromo-2-chloropyridin-4-yl)acetyl]piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866748964-[2-(5-Bromo-2-chloropyridin-4-yl)-1-hydroxy-ethyl]piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium borohydride (240 mg) is added to an ice-cooled solution of 4-[2-(5-bromo-2-chloro-pyridin-4-yl)-acetyl]-piperidine-1-carboxylic acid tert-butyl ester (1.65 g) in a mixture of tetrahydrofuran (40 mL) and water (10 mL). The resulting mixture stirred for 0.5 h. 2 N Citric acid is added and the mixture is extracted with ethyl acetate. The combined extracts are washed with aqueous NaHCO3 solution and brine, dried over MgSO4, and concentrated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 65:35) to give the title compound. LC (method 5): tR=1.48 min; Mass spectrum (ESI+): m/z=419, 421 [M+H]+.

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe combined extracts are washed with aqueous NaHCO3 solution and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 65:35)

Sources & evidence

ORD record
ord-75f0f46e9adc46309ae8060750896f28
Source dataset
uspto-grants-2014_07
Patent number
US08778926B2

Reaction notes

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