(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 1254260Notes

Reaction equation

HRID 1254260 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-6a3f88c8dc0e425f99dd884baa402c5d
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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