Potassium Hydroxide → (S)-1-N-Cbz-Pipecolinic acid

HRID 1826575Notes

Reaction equation

HRID 1826575 reaction equation
C[O:2][C:3]([C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][N:6]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:4].[OH-].[K+]>CO.O>[CH2:14]([O:13][C:11]([N:6]1[CH2:7][CH2:8][CH2:9][CH2:10][C@H:5]1[C:3]([OH:4])=[O:2])=[O:12])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 45072536S-Methyl 1-cbz-piperidine-2-carboxylate

Product 1

HCID 688345(S)-1-N-Cbz-Pipecolinic acidYield 100.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a stirred solution of (S)-piperidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester (8.0g, 28.8 mmol) in MeOH (75 mL ) and water (38 mL ) at 0° C. was added powdered KOH (1.78 g, 31.7 mmol). The reaction mixture was allowed to stir for 16 h at room temperature and then the MeOH was removed in vacuo. The residue was diluted with water and washed DCM. The aqueous layer was acidified with 1.0-M HCl and extracted with ethyl acetate three times. The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound as pale yellow oil (7.6 g, 100%): 1H NMR (400 MHz, CD3OD) δ 1.36–1.61 (2H, m), 1.70–1.85 (3H, m), 2.28–2.40 (1H, m), 3.05–3.26 (1H, m), 4.06–4.14 (1H, m), 4.89–5.26 (4H, m), 7.37–7.48 (5H, m); 13C NMR (100 MHz, CD3OD) δ 20.5, 20.6 (CH2), 24.6, 24.7 (CH2), 26.6 (CH2), 41.8, 41.9 (CH2), 54.5, 54.7 (CH), 67.2, 67.3 (CH2), 127.6 (CH), 127.9 (CH), 128.4 (CH), 136.9 (C), 173.4 (CO).

Workup

  1. customthe MeOH was removed in vacuo
  2. additionThe residue was diluted with water
  3. washwashed DCM
  4. extractionextracted with ethyl acetate three times
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ebb9b3478da144b68ebb605af0d8afbb
Source dataset
uspto-grants-2006_05
Patent number
US07053057B2

Reaction notes

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