Methanol → 3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-benzyl ester

HRID 1269509Notes

Reaction equation

HRID 1269509 reaction equation
[CH:1]([C:4]1[CH:39]=[CH:38][C:7]([CH2:8][O:9][C:10]([N:12]2[CH2:17][CH2:16][CH2:15][CH:14]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([C:28]([O:30]CC4C=CC=CC=4)=[O:29])([CH3:27])[CH3:26])[CH:19]=3)[CH2:13]2)=[O:11])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].CO>O>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][O:9][C:10]([N:12]2[CH2:17][CH2:16][CH2:15][CH:14]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([C:28]([OH:30])=[O:29])([CH3:27])[CH3:26])[CH:19]=3)[CH2:13]2)=[O:11])=[CH:38][CH:39]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 688826363-[3-(1-Benzyloxycarbonyl-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-benzyl ester

Product 1

HCID 100947333-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-benzyl esterYield 94%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 3-[3-(1-Benzyloxycarbonyl-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-benzyl ester (1.07 g, 2.02 mmol), potassium carbonate (0.56 g, 4.04 mmol), methanol (15 mL) and water (3 mL) was heated at reflux for 3 h, cooled to room temperature and concentrated under reduced pressure. The resulting residue was taken up in water (150 mL), acidified with 1N aqueous hydrochloric acid and extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was eluted through a 20 g plug of silica with 300 mL methylene chloride then 300 mL ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to yield 835 mg (94%) of 3-[3-(1-carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-benzyl ester as a clear glassy solid.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 h
  3. concentrationconcentrated under reduced pressure
  4. extractionextracted with ethyl acetate (2×100 mL)
  5. washThe combined organic extracts were washed with saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. washThe resultant oil was eluted through a 20 g plug of silica with 300 mL methylene chloride
  10. additionFractions containing product
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0713134b76d941f4aff741188693edc0
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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