(R)-1-(3-methylbutanoyl)piperidine-3-carboxylic acid → (R)-1-(3-(hydroxymethyl)piperidin-1-yl)-3-methylbutan-1-one

HRID 332994Notes

Reaction equation

HRID 332994 reaction equation
[CH3:1][CH:2]([CH3:15])[CH2:3][C:4]([N:6]1[CH2:11][CH2:10][CH2:9][C@@H:8]([C:12](O)=[O:13])[CH2:7]1)=[O:5]>C1COCC1>[OH:13][CH2:12][C@@H:8]1[CH2:9][CH2:10][CH2:11][N:6]([C:4](=[O:5])[CH2:3][CH:2]([CH3:1])[CH3:15])[CH2:7]1

Participants

3

Reactant 1

HCID 42257258(R)-1-(3-methylbutanoyl)piperidine-3-carboxylic acid

Product 1

HCID 28345459(R)-1-(3-(hydroxymethyl)piperidin-1-yl)-3-methylbutan-1-oneYield 7.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-1-(3-methylbutanoyl)piperidine-3-carboxylic acid (Example 34d) (2.52 g, 11.84 mmol) in THF (20 mL) at 0° C., was added BH3Me2S (1.2 mL, 13.0 mmol) dropwise over 15 minutes. The reaction was warmed to room temperature and stirred overnight, cooled to 0° C., quenched with water, concentrated under reduced pressure to remove THF and extracted with EtOAc. The combined extracts were washed with saturated aqueous NaHCO3, dried over Na2SO4, filtered, concentrated under reduced pressure and purified by flash chromatography on silica gel (EtOAc/hexanes) to give the title compound (184 mg, 6%). MS 200 (MH+).

Workup

  1. temperaturecooled to 0° C.
  2. customquenched with water
  3. concentrationconcentrated under reduced pressure
  4. customto remove THF
  5. extractionextracted with EtOAc
  6. washThe combined extracts were washed with saturated aqueous NaHCO3
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. custompurified by flash chromatography on silica gel (EtOAc/hexanes)

Sources & evidence

ORD record
ord-19be4ec9642447e781abc30f743457c0
Source dataset
uspto-grants-2014_11
Patent number
US08877922B2

Reaction notes

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