Pipecolic Acid → (S)-1-N-Cbz-Pipecolinic acid

HRID 1742750Notes

Reaction equation

HRID 1742750 reaction equation
[NH:1]1[CH2:9][CH2:8][CH2:7][CH2:6][CH:2]1[C:3]([OH:5])=[O:4].C(=O)([O-])[O-].[K+].[K+].Cl[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18]>O.C1COCC1>[N:1]1([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:9][CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4]

Participants

6

Reactant 3

HCID 849Pipecolic AcidHCID 10387Benzyl chloroformateHCID 11430Potassium Carbonate

Product 1

HCID 688345(S)-1-N-Cbz-Pipecolinic acidYield 75.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. suspension of pipecolic acid (0.15 g, 1.16 mmol) and potassium carbonate (4.64 mmol) in water (5 mL) and THF (5 mL) was added benzyl chloroformate (0.24 g, 1.41 mmol). The mixture was rapidly stirred for one hour then allowed to warm to ambient temperature. After 6 hours, the reaction was diluted with water and washed with ether. The aqueous layer was acidified and extracted with methylene chloride. The organic phase was washed with brine then dried over sodium sulfate. The solvent was evaporated and the residue recrystallized from hexane-ethyl acetate to yield 0.23 g (75% yield) of the title compound as a white solid. MS(CI) m/e 264 (M+H)+. 1H NMR (300 MHz, CDCl3) δ1.24-1.80 (m, 5H), 2.26 (br t, 1H), 2.93-3.14 (m, 1H), 4.00-4.19 (m, 1H), 4.87-5.05 (m, 1H), 5.15 (br s, 2H), 7.27-7.41 (m, 5H).

Workup

  1. waitAfter 6 hours
  2. washwashed with ether
  3. extractionextracted with methylene chloride
  4. washThe organic phase was washed with brine
  5. dry with materialthen dried over sodium sulfate
  6. customThe solvent was evaporated
  7. customthe residue recrystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-9990ec9c01b54e158b28587e3030d1e3
Source dataset
uspto-grants-1994_08
Patent number
US05340802

Reaction notes

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