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

HRID 1468759ノート

反応式

HRID 1468759 の反応式
[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

参加物

6

反応物 3

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

生成物 2

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-4fff014cbccd481b88797842ffa1f866
出典データセット
uspto-grants-2015_04
特許番号
US09006232B2

反応ノート

読み込み中…