Sulfuric Acid → (R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3,3-dimethyl-pyrrolidin-2-one

HRID 1500417

反応式

HRID 1500417 の反応式
[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[N:12]([C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[C:11](=[O:19])[C@H:10]([CH3:20])[CH2:9]2)=[CH:3][CH:2]=1.[CH:27]([N-]C(C)C)(C)C.[Li+].CI.NCCC(CN)O.S(=O)(=O)(O)O>C1COCC1>[C:1]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[N:12]([C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[C:11](=[O:19])[C:10]([CH3:27])([CH3:20])[CH2:9]2)=[CH:5][CH:6]=1

参加物

7

反応物 5

HCID 1118Sulfuric AcidHCID 6328Methyl iodideHCID 1646562-HydroxyputrescineHCID 2724682Lithium diisopropylamideHCID 66738857(3R,5S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-methylpyrrolidin-2-one

生成物 1

HCID 59318477(R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3,3-dimethyl-pyrrolidin-2-one

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-30 °C

実験手順

10 g (3R,5S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-methylpyrrolidin-2-one (2-a, R1=Piv) is added to THF (100 ml). The mixture is cooled to −30° C. Lithium diisopropylamide (17.16 ml, 2 M) is added and the mixture is stirred for 1 h. Methyl iodide (5.4 ml) is added and the mixture is stirred for 3 h. Aminoethylethanolamine (6.1 ml) is added and the mixture is warmed to 40° C. and stirred for 15 min. Sulphuric acid (12 g) is then added. The mixture is concentrated in vacuo and the residue taken up in toluene. The phases are separated. The organic phase is concentrated in vacuo and taken up in methanol (300 ml) at reflux. On cooling, the precipitate is collected by filtration to give (R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3,3-dimethyl-pyrrolidin-2-one. 1H NMR (DMSO): 1.04 (3H), 1.15 (3H), 1.28 (9H), 1.72 (1H), 1.38 (1H), 2.59 (1H), 3.14 (1H), 4.37 (1H), 7.31 (3H), 7.45 (2H), 7.62 (4H).

後処理

  1. stirringthe mixture is stirred for 3 h
  2. temperaturethe mixture is warmed to 40° C.
  3. stirringstirred for 15 min
  4. concentrationThe mixture is concentrated in vacuo
  5. customThe phases are separated
  6. concentrationThe organic phase is concentrated in vacuo
  7. temperatureat reflux
  8. temperatureOn cooling
  9. filtrationthe precipitate is collected by filtration

出典と根拠

ORDレコード
ord-c79134347f05476e81ef72a47a57c0ea
出典データセット
uspto-grants-2015_12
特許番号
US09206116B2

関連ノート

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