(3R)-1-(tert-butoxycarbonyl)-3-(2-phenoxybenzoyl)piperidine → (R)-tert-butyl 3-((S)-1-hydroxy-5-methoxy-1-(2-phenoxyphenyl)pentyl)piperidine-1-carboxylate

HRID 2355380Notes

Reaction equation

HRID 2355380 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14](=[O:28])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:29][O:30][CH2:31][CH2:32][CH2:33][CH2:34][Mg]Cl>C1COCC1>[OH:28][C@@:14]([C@@H:10]1[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[O:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[CH2:34][CH2:33][CH2:32][CH2:31][O:30][CH3:29]

Participants

4

Reactant 2

HCID 59382959(3R)-1-(tert-butoxycarbonyl)-3-(2-phenoxybenzoyl)piperidineHCID 178495008HCID 178495008, compound

Product 1

HCID 59382949(R)-tert-butyl 3-((S)-1-hydroxy-5-methoxy-1-(2-phenoxyphenyl)pentyl)piperidine-1-carboxylateYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (3R)-1-(tert-butoxycarbonyl)-3-(2-phenoxybenzoyl)piperidine (6.17 g, 16.2 mmol) in THF (30 mL) at −10° C. was added dropwise 2.54 M 4-methoxybutylmagnesium chloride in THF (15 mL, 38 mmol). The resulting solution was warmed to rt slowly, and stirred over night. The reaction was quenched with sat'd NH4Cl (10 mL) and extracted with Et2O (4×10 mL). The combined organic layers were washed with water and brine. The solvent was removed and the residue was purified by flash chromatography to give (R)-tert-butyl 3-((S)-1-hydroxy-5-methoxy-1-(2-phenoxyphenyl)pentyl)piperidine-1-carboxylate (1.97 g, 26% from (R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylate).

Workup

  1. customThe reaction was quenched with sat'd NH4Cl (10 mL)
  2. extractionextracted with Et2O (4×10 mL)
  3. washThe combined organic layers were washed with water and brine
  4. customThe solvent was removed
  5. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-25758e2ccdd649e591725088def96e89
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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