Pipecolic Acid → 1-(3-Benzyloxybenzoyl)-2-piperidinecarboxylic acid

HRID 1741393Notes

Reaction equation

HRID 1741393 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([OH:14])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(OCC(C)C)=O.[NH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]1[C:32]([OH:34])=[O:33].C([O-])(O)=O.[Na+]>C1COCC1.O.C(N(CC)CC)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([N:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]1[C:32]([OH:34])=[O:33])=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 849Pipecolic AcidHCID 62365Isobutyl chloroformateHCID 3092263-(Benzyloxy)benzoic acidHCID 516892Sodium Bicarbonate

Product 1

HCID 183674161-(3-Benzyloxybenzoyl)-2-piperidinecarboxylic acidYield 27%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

Triethylamine (3.36 ml) was added to a stirred solution of 3-benzyloxybenzoic acid (5.0 g) and isobutyl chloroformate (3.13 ml) in THF (67 ml) under ice-cooling and the resulting mixture was stirred at the same temperature for 1 hour. A solution of 2-piperidinecarboxylic acid (4.14 g) and NaHCO3 (3.32 g) in water (40 ml) was added dropwise to the stirred mixture at the same temperature and the mixture was stirred at the same temperature for 2 hours and at room temperature overnight. The reaction mixture was partitioned between ethyl acetate and 1N HCl. The organic layer was separated, washed with 1N HCl (twice) and brine, dried over MgSO4, and evaporated in vacuo. The residue was chromatographed over silica gel to afford 1-(3-benzyloxybenzoyl)-2-piperidinecarboxylic acid (2.01 g) as a amorphous powder. (+) APCI-MS (m/z): 340 (M+ +1) IR (Nujol): 2590, 1710, 1595, 1575, 1230 cm-1

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at the same temperature for 2 hours and at room temperature overnight
  3. customThe reaction mixture was partitioned between ethyl acetate and 1N HCl
  4. customThe organic layer was separated
  5. washwashed with 1N HCl (twice) and brine
  6. dry with materialdried over MgSO4
  7. customevaporated in vacuo
  8. customThe residue was chromatographed over silica gel

Sources & evidence

ORD record
ord-58ab10d917304b01879cc7c989342a00
Source dataset
uspto-grants-1999_10
Patent number
US05972965

Reaction notes

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