Borane;tetrahydrofuran → 1-Boc-4-(hydroxymethyl)-4-methylpiperidine

HRID 1677428Notes

Reaction equation

HRID 1677428 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH3:17])([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B.C1COCC1>C1COCC1>[NH4+:8].[OH-:5].[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:14][OH:15])([CH3:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 2723981Borane;tetrahydrofuran2×HCID 232828481-[(Tert-butoxy)carbonyl]-4-methylpiperidine-4-carboxylic acid

Product 2

HCID 14923Ammonium HydroxideHCID 232828431-Boc-4-(hydroxymethyl)-4-methylpiperidineYield 101.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. solution of 4-methyl-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (5 g, 20.6 mmol) in THF (70 mL) was added dropwise over 20 min BH3.THF (31 mL, 1 M solution in THF, 31 mmol). The resultant reaction was allowed to warm slowly to room temperature, stirred at room temperature overnight, stirred at reflux for 4.5 h, allowed to cool to room temperature, treated with additional BH3.THF (30 mL, 1 M solution in THF, 30 mmol), and stirred at room temperature overnight. The reaction was divided into two batches and each was quenched with saturated NaHCO3 and extracted with EtOAc and the organic phase was dried over Na2SO4 and concentrated. The crude product from one batch was purified by flash chromatography using 110 g of silica gel and 0-50% of 9.5:0.5 MeOH:conc NH4OH in CH2Cl2 as eluant to afford 2.4 g of 4-hydroxymethyl-4-methyl-piperidine-1-carboxylic acid tert-butyl ester as a colorless oil.

Workup

  1. customThe resultant reaction
  2. stirringstirred
  3. temperatureat reflux for 4.5 h
  4. temperatureto cool to room temperature
  5. stirringstirred at room temperature overnight
  6. customeach was quenched with saturated NaHCO3
  7. extractionextracted with EtOAc
  8. dry with materialthe organic phase was dried over Na2SO4
  9. concentrationconcentrated
  10. customThe crude product from one batch was purified by flash chromatography

Sources & evidence

ORD record
ord-2357852af3004adf9332833312bcbb54
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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