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

HRID 580846노트

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HRID 580846 반응식
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]

참가 물질

8

반응물 5

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매3회

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온도
-70 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-a5cad137e9d14b72bd55cd76c795f3f0
출처 데이터셋
uspto-grants-1999_07
특허 번호
US05919781

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