p-Toluenesulfonic acid → (R)-methyl 5-oxo-1-((R)-1-phenylethyl)pyrrolidine-3-carboxylate

HRID 1468759노트

반응식

HRID 1468759 반응식
[C:1]([O:10][CH3:11])(=[O:9])[C:2]([CH2:4][C:5](OC)=[O:6])=[CH2:3].[C:12]1([C@H:18]([NH2:20])[CH3:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[O:6]=[C:5]1[N:20]([C@@H:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:19])[CH2:3][C@@H:2]([C:1]([O:10][CH3:11])=[O:9])[CH2:4]1.[O:6]=[C:5]1[N:20]([C@@H:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:19])[CH2:3][C@H:2]([C:1]([O:10][CH3:11])=[O:9])[CH2:4]1

참가 물질

6

반응물 3

HCID 6101p-Toluenesulfonic acidHCID 69240Dimethyl itaconateHCID 6431891-Phenethylamine, (+)-

생성물 2

HCID 11637375(R)-methyl 5-oxo-1-((R)-1-phenylethyl)pyrrolidine-3-carboxylate수율 48%HCID 13772852Methyl (3S)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate수율 36%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

To a solution of dimethyl itaconate (25 g, 158 mmol) in methanol (150 ml) was added (R)-1-phenylethylamine (20 ml, 158 mmol) at room temperature. The resulting mixture was stirred for 18 hours and concentrated. The residue was dissolved in toluene (100 ml) and p-toluenesulfonic acid (3.0 g, 16 mmol) was added at room temperature. The mixture was refluxed for 16 hours and concentrated. The residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=1/1 to 1/3) to afford methyl (3S)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate as a white solid (14.0 g, 56.5 mmol, 36%) and methyl (3R)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate as a yellow oil (18.7 g, 75.5 mmol, 48%). Each stereochemistry was determined by the data based on the literature (J. Med. Chem. 1990, 33, 71-77).

후처리

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in toluene (100 ml)
  3. temperatureThe mixture was refluxed for 16 hours
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=1/1 to 1/3)

출처 및 근거

ORD 기록
ord-4fff014cbccd481b88797842ffa1f866
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006232B2

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