Isovaleryl chloride → (R)-1-(3-methylbutanoyl)piperidine-3-carboxylic acid

HRID 332995Notes

Reaction equation

HRID 332995 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([C:7]([OH:9])=[O:8])[CH2:2]1.C([O-])(O)=O.[Na+].[CH3:15][CH:16]([CH3:21])[CH2:17][C:18](Cl)=[O:19]>O.C1COCC1>[CH3:15][CH:16]([CH3:21])[CH2:17][C:18]([N:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([C:7]([OH:9])=[O:8])[CH2:2]1)=[O:19]

Participants

6

Reactant 3

HCID 66054Isovaleryl chlorideHCID 516892Sodium BicarbonateHCID 1796510(-)-Nipecotic acid

Product 1

HCID 42257258(R)-1-(3-methylbutanoyl)piperidine-3-carboxylic acidYield 76.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-piperidine-3-carboxylic acid (2.0 g, 15.48 mmol) in water (40 mL) and THF (20 mL) were added NaHCO3 (3.30 g, 38.70 mmol) and 3-methylbutanoyl chloride (2.8 mL, 23.2 mmol) at room temperature. The reaction was stirred overnight, concentrated under reduced pressure, diluted with water (50 mL) and extracted with EtOAc (1×). The aqueous layer was acidified with 1N HCl, extracted with EtOAc (3×) and the combined extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound (2.53 g, 76%). MS 214 (MH+).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additiondiluted with water (50 mL)
  3. extractionextracted with EtOAc (1×)
  4. extractionextracted with EtOAc (3×)
  5. dry with materialthe combined extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bd3d9890c8ac4734b976284c3cc1b32f
Source dataset
uspto-grants-2014_11
Patent number
US08877922B2

Reaction notes

Loading…