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

HRID 580846ノート

反応式

HRID 580846 の反応式
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]

参加物

8

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒3 回

反応条件

温度
-70 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-a5cad137e9d14b72bd55cd76c795f3f0
出典データセット
uspto-grants-1999_07
特許番号
US05919781

反応ノート

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