Sodium Hydroxide → 3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1269485Notes

Reaction equation

HRID 1269485 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([OH:20])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH2:21].Cl[C:23](Cl)(Cl)[C:24]([CH3:27])(O)[CH3:25].[OH-:30].[Na+]>CC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:24]([C:23]([OH:30])=[O:21])([CH3:25])[CH3:27])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 122198322-Propanol, 1,1,1-trichloro-2-methyl-, hydrateHCID 688844513-(3-Hydroxyphenyl)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 688861023-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
0 °C

Procedure

3-(3-Hydroxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (17.03 g, 61.39 mmol) was dissolved in 420 mL acetone in a 3-neck 1 L round bottom flask equipped with a mechanical stirrer. 1,1,1-trichloro-2-methyl-2-propanol hydrate (21.80 g, 122.78 mmol) was added and the solution was cooled to 0° C. Sodium hydroxide pellets (19.65 g, 491.12 mmol) were added to the solution at 0° C. over 4 h in four portions. The reaction mixture warmed to ambient temperature between additions and then recooled. Once the additions were complete, the reaction mixture was allowed to stir at ambient temperature for 24 h and then concentrated under reduced pressure. The resulting residue was taken up in water (500 mL), acidified with 6N aqueous hydrochloric acid, stirred 10 min and then extracted with ethyl acetate (3×300 mL). The combined organics were washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to provide 3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester as a brown oil which was taken on to the next step without further purification.

Workup

  1. customequipped with a mechanical stirrer
  2. additionwere added to the solution at 0° C. over 4 h in four portions
  3. temperatureThe reaction mixture warmed to ambient temperature between additions
  4. concentrationconcentrated under reduced pressure
  5. stirringstirred 10 min
  6. extractionextracted with ethyl acetate (3×300 mL)
  7. washThe combined organics were washed with saturated aqueous sodium chloride
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e5f0fea7185e400e900f4b1fdacec9fa
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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