Ammonium Chloride → tert-Butyl 4-hydroxy-3-(hydroxymethyl)piperidine-1-carboxylate

HRID 1971938Notes

Reaction equation

HRID 1971938 reaction equation
C([O:3][C:4]([CH:6]1[C:11](=[O:12])[CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7]1)=O)C.[BH4-].[Na+].[NH4+].[Cl-]>CO>[C:16]([O:15][C:13]([N:8]1[CH2:9][CH2:10][CH:11]([OH:12])[CH:6]([CH2:4][OH:3])[CH2:7]1)=[O:14])([CH3:19])([CH3:18])[CH3:17]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 64208761-(1,1-Dimethylethyl) 3-ethyl 4-oxo-1,3-piperidinedicarboxylate

Product 1

HCID 66717856tert-Butyl 4-hydroxy-3-(hydroxymethyl)piperidine-1-carboxylateYield 84.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 4-oxo-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (14 g) in MeOH (300 mL) was added NaBH4 (12 g) in 12 lots over 1 h period. After completion of addition, the reaction mixture was stirred for 30 min. Removed solvent under reduced pressure, to the residue was added saturated NH4Cl solution (300 mL) and was extracted with EtOAc (300 mL). The organic layer was dried, filtered and concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography by eluting with ethyl acetate to give 4-hydroxy-3-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (10.1 g, cis/trans mixture).

Workup

  1. additionAfter completion of addition
  2. extractionwas extracted with EtOAc (300 mL)
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash silica gel column chromatography
  7. washby eluting with ethyl acetate

Sources & evidence

ORD record
ord-3323d63645c64617abca9eb7f80ad5d3
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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