1-Boc-2-phenyl-piperidin-4-one → (+/-)-tert-butyl (2R,4S)-4-methyl-2-phenylpiperidin-4-ol-1-carboxylate

HRID 473810Notes

Reaction equation

HRID 473810 reaction equation
[CH3:1][Mg]Br.[O:4]=[C:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:6]1>O1CCCC1>[CH3:1][C@:5]1([OH:4])[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@@H:7]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:6]1

Participants

4

Reactant 2

HCID 445586011-Boc-2-phenyl-piperidin-4-oneHCID 178418573HCID 178418573, compound

Product 1

HCID 131731160(+/-)-tert-butyl (2R,4S)-4-methyl-2-phenylpiperidin-4-ol-1-carboxylateYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methylmagnesium bromide (3 M solution in ether, 1.2 mL, 3.6 mmol) was added to a solution of tert-butyl 4-oxo-2-phenylpiperidine-1-carboxylate (328 mg, 1.2 mmol), in tetrahydrofuran (20 mL) at 0° C. and the resulting mixture was stirred at this temperature one hour. The reaction mixture was then quenched with saturated aqueous ammonium chloride solution (20 mL) and diluted with ethyl acetate (80 mL). The organic portion was separated, washed with water, then brine solution, dried over sodium sulfate, filtered and concentrated. The residue purified by silica gel chromatography (25% to 70% ethyl acetate in hexane gradient) to give the first eluting isomer assigned as (±)-tert-butyl (2R,4S)-4-methyl-2-phenylpiperidin-4-ol-1-carboxylate (100 mg, 29% yield), LC-MS for C17H25NO3: 292 (MH+); and the second eluting isomer assigned as (±)-tert-butyl (2R,4R)-4-methyl-2-phenylpiperidin-4-ol-1-carboxylate (120 mg, 35% yield), MS (EI) for C17H25NO3: 292 (MH+).

Workup

  1. customThe reaction mixture was then quenched with saturated aqueous ammonium chloride solution (20 mL)
  2. additiondiluted with ethyl acetate (80 mL)
  3. customThe organic portion was separated
  4. washwashed with water
  5. dry with materialbrine solution, dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue purified by silica gel chromatography (25% to 70% ethyl acetate in hexane gradient)
  9. customto give the first eluting isomer

Sources & evidence

ORD record
ord-fe500fa04b8d44a981d9c4a6a2ed3dcc
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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