Tert-butyl 3-benzoylpiperidine-1-carboxylate → Tert-butyl 3-(1-hydroxy-1-phenylheptyl)piperidine-1-carboxylate

HRID 2355307Notes

Reaction equation

HRID 2355307 reaction equation
[C:1]([CH:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:22]([Mg]Br)[CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]>C1COCC1>[OH:8][C:1]([CH:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]

Participants

4

Reactant 2

HCID 57449677Tert-butyl 3-benzoylpiperidine-1-carboxylateHCID 178444609HCID 178444609, compound

Product 1

HCID 59382974Tert-butyl 3-(1-hydroxy-1-phenylheptyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To a 100-mL round bottom flask were added tert-butyl 3-(benzoyl)piperidine-1-carboxylate (0.4733 g, 1.63 mmol, 1.0 equiv) and THF (5 mL). The flask was evacuated and refilled with N2. The mixture was cooled with a dry ice-acetone bath and hexylmagnesium bromide (2.0M solution in Et2O, 2.5 mL, 5.0 mmol, 3.0 equiv) was added. The reaction mixture was allowed to slowly warm to −10° C. while stirring overnight (17 h). The mixture was quenched with saturated NH4Cl (10 mL), extracted three times with EtOAc, and dried over Na2SO4. The crude product was purified by reversed-phase HPLC (XTerra® Prep MS C18 OBD™ Column, 5 μm, 19×50 mm, 10%→90% CH3CN/H2O, 0.1% CF3COOH over 8 min, flow rate 20 mL/min) to give tert-butyl 3-(1-hydroxy-1-phenylheptyl)piperidine-1-carboxylate. LC-MS (3 min) tR=2.41 min, m/z 398 (M+Na+), 376 (MH+), 302, 276, 258.

Workup

  1. customThe flask was evacuated
  2. additionrefilled with N2
  3. temperatureThe mixture was cooled with a dry ice-acetone bath
  4. customThe mixture was quenched with saturated NH4Cl (10 mL)
  5. extractionextracted three times with EtOAc
  6. dry with materialdried over Na2SO4
  7. customThe crude product was purified by reversed-phase HPLC (XTerra® Prep MS C18 OBD™ Column, 5 μm, 19×50 mm, 10%→90% CH3CN/H2O, 0.1% CF3COOH over 8 min, flow rate 20 mL/min)

Sources & evidence

ORD record
ord-8e6d3016dd7d49768cc80108fed3ec65
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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