Lithium Hydroxide → 2-[1-(Tert-butoxycarbonyl)piperidin-4-yl]propanoic acid

HRID 238235Notes

Reaction equation

HRID 238235 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([C:16]([O:18]C)=[O:17])[CH3:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-]>O.C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([C:16]([OH:18])=[O:17])[CH3:15])[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 184234934-(1-Methoxycarbonyl-ethyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 177818912-[1-(Tert-butoxycarbonyl)piperidin-4-yl]propanoic acidYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-(1-methoxycarbonylethyl)-piperidine-1-carboxylic acid tert-butyl ester (40 g crude from last step, about 0.15 mol), LiOH (12.6 g, 0.3 mol) in water (200 mL) and THF (400 mL) was heated to reflux for 4 hours. The cooled mixture was diluted with water (200 mL) and washed with Et2O (200 mL×2). The aqueous layer was acidified with HCl (10%) at 0° C. to pH3-4. The mixture was extracted with Et2O (200 mL×3) and the combined extracts were washed with brine, dried and concentrated to give the product as a white solid (28 g, 73% from N-benzyl-4-piperidone). 1HNMR (CDCl3) δ 4.11 (m, 2H), 2.69-2.63 (m, 2H), 2.30 (p, 1H, J=7.2 Hz), 1.72-1.62 (m, 3H), 1.44 (s, 9H), 1.27-1.18 (m, 2H), 1.16 (d, 3H, J=7.2 Hz).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 4 hours
  3. washwashed with Et2O (200 mL×2)
  4. customwas acidified with HCl (10%) at 0° C. to pH3-4
  5. extractionThe mixture was extracted with Et2O (200 mL×3)
  6. washthe combined extracts were washed with brine
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-7a61e420836c4859b1ebf8d8700af040
Source dataset
uspto-grants-2014_02
Patent number
US08642609B2

Reaction notes

Loading…