Phenylacetic Acid → 4-Hydroxy-4-(1-carboxy-1-phenyl-methyl)piperidine-1-carboxylic acid tert-butyl ester

HRID 606757Notes

Reaction equation

HRID 606757 reaction equation
[C:1]1([CH2:7][C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Mg]Cl)(C)C.[C:16]([N:23]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1)([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17]>C1COCC1>[C:19]([O:18][C:16]([N:23]1[CH2:28][CH2:27][C:26]([OH:29])([CH:7]([C:8]([OH:10])=[O:9])[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:25][CH2:24]1)=[O:17])([CH3:22])([CH3:20])[CH3:21]

Participants

5

Reactant 3

HCID 999Phenylacetic AcidHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 670465474-Hydroxy-4-(1-carboxy-1-phenyl-methyl)piperidine-1-carboxylic acid tert-butyl esterYield 99.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of phenylacetic acid (13.7 g, 0.100 mol) in THF (90 mL) at 0° C. was slowly added iPrMgCl (2M in Et2O, 100 mL, 0.200 mol). The mixture was stirred at rt for 1 h and then N-Boc-4-piperidone (20.0 g, 0.100 mol) was added as a solid. Stirring was continued for 1 h and then the mixture was quenched with sat. NH4Cl and acidified to pH 2 using concentrated HCl. The mixture was extracted with EtOAc (×3) and the combined organic layers were dried over Na2SO4, filtered and concentrated to give the title compound (33.3 g, 99%) as a colorless foam which was of sufficient purity to continue to the next step:

Workup

  1. customat 0° C.
  2. stirringStirring
  3. waitwas continued for 1 h
  4. customthe mixture was quenched with sat. NH4Cl
  5. extractionThe mixture was extracted with EtOAc (×3)
  6. dry with materialthe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-a25a1098f7754ee4a87742796b17ff06
Source dataset
uspto-grants-2011_03
Patent number
US07915283B2

Reaction notes

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