(3R)-1-(tert-butoxycarbonyl)-3-((3-fluorophenoxy)benzoyl)piperidine → (R)-tert-butyl 3-((S)-1-(2-(3-fluorophenoxy)phenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylate

HRID 1254264Notes

Reaction equation

HRID 1254264 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14](=[O:29])[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]=[C:24]([F:28])[CH:23]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:30][O:31][CH2:32][CH2:33][CH2:34][CH2:35][Mg]Cl>C1COCC1>[F:28][C:24]1[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=1)[O:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[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)([OH:29])[CH2:35][CH2:34][CH2:33][CH2:32][O:31][CH3:30]

Participants

4

Reactant 2

HCID 59382815(3R)-1-(tert-butoxycarbonyl)-3-((3-fluorophenoxy)benzoyl)piperidineHCID 178495008HCID 178495008, compound

Product 1

HCID 59382895(R)-tert-butyl 3-((S)-1-(2-(3-fluorophenoxy)phenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylateYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (3R)-1-(tert-butoxycarbonyl)-3-((3-fluorophenoxy)benzoyl)piperidine (0.95 g, 2.37 mmol) in THF (3 mL) at −20° C. was added 1.45 M 4-methoxybutyl magnesium chloride in THF (3.3 mL, 4.76 mmol) dropwise. The resulting solution was warmed to rt slowly, and the completion of reaction was confirmed by LC-MS (˜20 min). The reaction was quenched with sat'd aq NH4Cl (4 mL) and extracted with Et2O (4×5 mL). The combined organic layers were washed with water and brine, and the solvent was removed in vacuo to give a crude product which was purified by flash column chromatography to afford (R)-tert-butyl 3-((S)-1-(2-(3-fluorophenoxy)phenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylate (0.50 g, 43%).

Workup

  1. customthe completion of reaction
  2. customwas confirmed by LC-MS (˜20 min)
  3. customThe reaction was quenched with sat'd aq NH4Cl (4 mL)
  4. extractionextracted with Et2O (4×5 mL)
  5. washThe combined organic layers were washed with water and brine
  6. customthe solvent was removed in vacuo
  7. customto give a crude product which
  8. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-4ceac032b18f404b8189bb1ad0d00df2
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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