Dimethyl Sulfoxide → tert-Butyl 3-oxo-2-phenylpiperidine-1-carboxylate

HRID 1166078Notes

Reaction equation

HRID 1166078 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH2:21][C@H:20]([OH:24])[C@@H:19]1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C.C(=O)([O-])O.[Na+]>ClCCl.O>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH2:21][C:20](=[O:24])[CH:19]1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

8

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 10901890(2S,3S)-1-t-Butyloxycarbonyl-3-hydroxy-2-phenylpiperidine

Product 1

HCID 11414684tert-Butyl 3-oxo-2-phenylpiperidine-1-carboxylateYield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-70 °C

Procedure

Dimethyl sulfoxide (32.0 mL, 35.3 g, 0.45 mol) in dichloromethane (100 mL) was added dropwise to a cooled (−70° C.) solution of oxalyl chloride (18.7 mL, 27.5 g, 0.22 mol) in dichloromethane (1000 mL). The mixture was stirred at −70° C. for 15 min., then (2S,3S)-1-tert-butoxycarbonyl-3-hydroxy-2-phenylpiperidine (prepared by the method described in European Patent Specification number 0 528 495-A; 50 g, 0.18 mol) in dichloromethane (150 mL) was added dropwise. The mixture was stirred at −70° C. for 1 h., then triethylamine (125.8 mL, 91.3 g, 0.9 mol) was added slowly. The mixture was stirred at room temperature for 1 h., water (250 mL) and aqueous sodium hydrogen carbonate (saturated, 250 mL) were added and the mixture was stirred at room temperature overnight. The layers were separated and the aqueous layer was extracted with dichloromethane (2×300 mL). The combined organic fractions were washed with brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/EtOAc (90:10), to give the title compound as a yellow oil (45.0 g, 91%). 1H NMR (250 MHz, CDCl3) δ 7.5-7.3 (5H, m), 5.8 (1H, br s), 4.2 (1H, br s), 3.4 (1H, m), 2.6 (2H, m), 2.0 (2H, m), and 1.54 (9H, s).

Workup

  1. stirringThe mixture was stirred at −70° C. for 1 h.
  2. stirringThe mixture was stirred at room temperature for 1 h.
  3. stirringthe mixture was stirred at room temperature overnight
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with dichloromethane (2×300 mL)
  6. washThe combined organic fractions were washed with brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by flash column chromatography on silica gel
  10. washeluting with hexane/EtOAc (90:10)

Sources & evidence

ORD record
ord-655571290d674766be096aacc076c5dd
Source dataset
uspto-grants-2003_09
Patent number
US06613765B1

Reaction notes

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