Bromoacetonitrile → ((S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidin-1-yl)acetonitrile

HRID 1641652ノート

反応式

HRID 1641652 の反応式
[C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[N:12]([C:13](=O)[C:14](C)(C)C)[C:11](=[O:19])[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.C([Li])CCC.BrCC#[N:34]>C1COCC1.CCCCCC>[C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]2[CH2:9][CH2:10][C:11](=[O:19])[N:12]2[CH2:13][C:14]#[N:34])=[CH:3][CH:2]=1

参加物

6

反応物 3

HCID 11534BromoacetonitrileHCID 58160363(S)-5-[(biphenyl-4-yl)methyl]-1-(2,2-dimethylpropionyl)pyrrolidin-2-oneHCID 178418339Butyllithium

生成物 1

HCID 59318474((S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidin-1-yl)acetonitrile

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒

反応条件

温度
-78 °C

実験手順

1.5 g (5.97 mmol) (S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (1, R1═H) is dissolved in 15 ml dry THF and cooled to −78° C. After the addition of 4.13 ml butyl lithium in hexane (1.59 M) the yellow solution is stirred at −78° C. for 30 min. Subsequently, 475 μl (855 mg, 7.16 mmol) bromoacetonitrile is added and the mixture is warmed up to room temperature overnight. The reaction is then quenched on addition of 10 ml saturated NH4Cl solution followed by the addition of 6 ml water and the mixture is extracted with 2×40 ml ethyl acetate. The combined organic layers are separated, dried over MgSO4, filtered and evaporated. The resulting residue is purified by column chromatography (dichloromethane:methanol=99:1) to give ((S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidin-1-yl)acetonitrile (1-a, R1=cyanomethyl) as off-white solid. NMR (400 MHz, DMSO-d6, δ/ppm): 7.65 (m, 4H); 7.47 (t, J=7.4, 2H); 7.40 (m, 3H); 4.57 (d, J=17.7, 1H); 4.44 (d, J=17.7, 1H); 3.91 (m, 1H); 3.19 (dd, J=3.9, 13.8, 1H); 2.70 (dd, J=9.2, 13.8, 1H); 2.18 (m, 2H); 1.95 (m, 1H); 1.77 (m, 1H). MS (ESI, m/e) 291 [M+H]+. IR (solution in CH2Cl2, ν/cm−1): 3025; 2985; 2257; 1697; 1688; 1486; 1421; 1323; 1271; 1182; 760; 699.

後処理

  1. temperaturethe mixture is warmed up to room temperature overnight
  2. customThe reaction is then quenched on addition of 10 ml saturated NH4Cl solution
  3. additionfollowed by the addition of 6 ml water
  4. extractionthe mixture is extracted with 2×40 ml ethyl acetate
  5. customThe combined organic layers are separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe resulting residue is purified by column chromatography (dichloromethane:methanol=99:1)

出典と根拠

ORDレコード
ord-e2f8965d34c04cebb54e34d691501d65
出典データセット
uspto-grants-2012_02
特許番号
US08115016B2

反応ノート

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