Cesium carbonate → 3-[3-(1-Ethoxycarbonyl-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid benzyl ester

HRID 1269537Notes

Reaction equation

HRID 1269537 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([OH:24])[CH:18]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:31]([O:33][C:34](=[O:39])[C:35](Br)([CH3:37])[CH3:36])[CH3:32]>CN(C)C=O.O>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([O:24][C:35]([C:34]([O:33][CH2:31][CH3:32])=[O:39])([CH3:37])[CH3:36])[CH:18]=2)[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 688838223-(3-Hydroxy-4-methyl-phenyl)-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 688825133-[3-(1-Ethoxycarbonyl-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid benzyl esterYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-(3-hydroxy-4-methyl-phenyl)-piperidine-1-carboxylic acid benzyl ester (2.24 g, 6.88 mmol) in 15 mL dimethylformamide was added cesium carbonate (4.49 g, 13.77 mmol) and ethyl-2-bromoisobutyrate (4.04 mL, 27.53 mmol). The mixture was heated to 60° C. under N2 with stirring for 18 h and cooled to ambient temperature. The resultant brown suspension was diluted with 300 mL water and extracted with diethyl ether (2×200 mL). The organic phases were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 20% ethyl acetate/hexanes to yield 1.36 g (45%) of the desired 3-[3-(1-ethoxycarbonyl-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid benzyl ester as a clear oil.

Workup

  1. temperaturecooled to ambient temperature
  2. extractionextracted with diethyl ether (2×200 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customchromatographed with 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-9584f043fea04e799c2a196fb5df4a3b
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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