4-Acetyl-4-(4-chloro-phenyl)-piperidine-1-carboxylic acid tert-butyl ester → 4-(4-Chloro-phenyl)-4-(1-hydroxy-1-methyl-ethyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 917102Notes

Reaction equation

HRID 917102 reaction equation
[CH3:1][Mg]Br.[C:4]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]([C:24](=[O:26])[CH3:25])([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:13][CH2:12]1)=[O:10])([CH3:7])([CH3:6])[CH3:5]>C1(C)C=CC=CC=1.O1CCCC1.O1CCCC1>[C:4]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)([C:24]([OH:26])([CH3:1])[CH3:25])[CH2:13][CH2:12]1)=[O:10])([CH3:7])([CH3:5])[CH3:6]

Participants

5

Reactant 2

HCID 667581294-Acetyl-4-(4-chloro-phenyl)-piperidine-1-carboxylic acid tert-butyl esterHCID 178418573HCID 178418573, compound

Product 1

HCID 667585124-(4-Chloro-phenyl)-4-(1-hydroxy-1-methyl-ethyl)-piperidine-1-carboxylic acid tert-butyl esterYield 67%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a dry round bottom flask was added via syringe 16 ml methyl magnesium bromide in toluene/tetrahydrofuran (75:25, 1.4 M). The flask was cooled in an ice bath under a stream of nitrogen. A solution 4-acetyl-4-(4-chloro-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (337 mg, 1.02 mmol) in 5 ml tetrahydrofuran was added dropwise to the flask over 20 minutes and the resulting mixture was stirred at 0° C. for 8 hours. The reaction mixture was warmed to room temperature and stirred for 5 days. The reaction was quenched by slow addition of 150 ml saturated aqueous ammonium chloride and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over magnesium sulfate and concentrated under vacuum. The yellow residue was purified by silica gel chromatography, eluting with hexane-ethyl acetate (7.5:2.5) to give the title compound (242 mg, 67%).

Workup

  1. temperatureThe flask was cooled in an ice bath under a stream of nitrogen
  2. temperatureThe reaction mixture was warmed to room temperature
  3. stirringstirred for 5 days
  4. customThe reaction was quenched by slow addition of 150 ml saturated aqueous ammonium chloride
  5. extractionextracted with ethyl acetate
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under vacuum
  9. customThe yellow residue was purified by silica gel chromatography
  10. washeluting with hexane-ethyl acetate (7.5:2.5)

Sources & evidence

ORD record
ord-d2419a1c1a4346c0b6dffb420d1979e2
Source dataset
uspto-grants-2007_09
Patent number
US07271176B2

Reaction notes

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