m-Chloroperbenzoic acid → Tert-butyl 4-fluoro-4-phenylpiperidine-1-carboxylate

HRID 1411401Notes

Reaction equation

HRID 1411401 reaction equation
C(N(S(F)(F)[F:7])CC)C.C(=O)=O.CC(C)=O.O[C:18]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1.ClC1C=C(C=CC=1)C(OO)=O>ClCCl>[F:7][C:18]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1

Participants

6

Reactant 4

HCID 70297m-Chloroperbenzoic acidHCID 123472(Diethylamino)sulfur trifluorideHCID 11231242Tert-butyl 4-hydroxy-4-phenylpiperidine-1-carboxylateHCID 18522661Acetone cardice

Product 1

HCID 59050060Tert-butyl 4-fluoro-4-phenylpiperidine-1-carboxylateYield 102.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of diethylaminosulfur trifluoride (4 mL, 32.7 mmol) in dichloromethane (10 mL) was added to a cold (−78° C.; dry ice/acetone bath) solution of tert-butyl 4-hydroxy-4-phenylpiperidine-1-carboxylate (8.05 g, 29.0 mmol) in dichloromethane (100 mL) under nitrogen. The reaction was stirred at −78° C. for ˜1 hour. The reaction was removed from the bath and warmed to ambient temperature then stirred another 30 minutes. The reaction was quenched with saturated aqueous NaHCO3 (100 mL). The organic fraction was washed with brine (˜50 mL). Then 3-chloroperoxybenzoic acid (1.0995 g, 6.37 mmol) was added to the reaction and stirred at ambient temperature for 30 minutes. This step was quenched with saturated aqueous NaHCO3 (100 mL). The organic fraction was washed with saturated aqueous NaHCO3 (1×100 mL), water (1×100 mL), and brine (1×100 mL), dried (MgSO4), tested for peroxide (3-10 ppm) and concentrated to light yellow oil. The oil was dried under vacuum to afford 8.27 g (100%) of the titled compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.42 (d, J=5.7, 9H), 1.96-1.85 (m, 3.5H), 2.03 (ddd, J=5.2, 13.3, 17.8, 1.5H), 3.06 (s, 2H), 3.98 (d, J=12.0, 2H), 7.33 (d, J=7.1, 1H), 7.46-7.36 (m, 4H); MS (DCI) m/z 280 (M+H+, 60%), 297 (M+NH4+, 100%).

Workup

  1. customThe reaction was removed from the bath
  2. temperaturewarmed to ambient temperature
  3. stirringthen stirred another 30 minutes
  4. customThe reaction was quenched with saturated aqueous NaHCO3 (100 mL)
  5. washThe organic fraction was washed with brine (˜50 mL)
  6. stirringstirred at ambient temperature for 30 minutes
  7. customThis step was quenched with saturated aqueous NaHCO3 (100 mL)
  8. washThe organic fraction was washed with saturated aqueous NaHCO3 (1×100 mL), water (1×100 mL), and brine (1×100 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated to light yellow oil
  11. customThe oil was dried under vacuum

Sources & evidence

ORD record
ord-868bb904b95b4382b9af52dd7ddcf85e
Source dataset
uspto-grants-2014_12
Patent number
US08921514B2

Reaction notes

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