Ethyl bromoacetate → [7a-(4-Cyano-benzyl)-3-(3,5-Dichlorophenyl)-2-oxo-2,3,5,6,7,7a-hexahydro-benzimidazol-3a-yl]-acetic acid ethyl ester

HRID 488741ノート

反応式

HRID 488741 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]3=[CH:14][CH2:15][CH2:16][CH2:17][C:12]3([CH2:18][C:19]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=3)[NH:11][C:10]2=[O:27])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[H-].[Na+].Br[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33]>CN(C=O)C>[CH2:35]([O:34][C:32](=[O:33])[CH2:31][C:13]12[CH2:14][CH2:15][CH2:16][CH2:17][C:12]1([CH2:18][C:19]1[CH:20]=[CH:21][C:22]([C:23]#[N:24])=[CH:25][CH:26]=1)[NH:11][C:10](=[O:27])[N:9]2[C:4]1[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=1)[CH3:36]

参加物

5

反応物 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 104534514-[1-(3,5-Dichlorophenyl)-2-oxo-1,2,3,4,5,6-hexahydro-benzimidazol-3a-ylmethyl]benzonitrile

生成物 1

HCID 69786744[7a-(4-Cyano-benzyl)-3-(3,5-Dichlorophenyl)-2-oxo-2,3,5,6,7,7a-hexahydro-benzimidazol-3a-yl]-acetic acid ethyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

4-[1-(3,5-Dichlorophenyl)-2-oxo-1,2,3,4,5,6-hexahydro-benzimidazol-3a-ylmethyl]benzonitrile (150 mg) (0.38 mmol) in DMF (5 ml) was carefully dropped on a suspension of NaH 60% (18.2 mg) (1.2 eq) in DMF (5 ml) at RT. The reaction mixture was stirred for 1 h at RT, then ethyl bromoacetate (0.052 ml) (1.2 eq) was added. After one night, the reaction mixture was poured on water and extracted with tBuOMe. The organic layer was washed with water, dried over Na2SO4 and concentrated. The residue was purified on SiO2 chromatography (eluent EtOAc/cyclohexane—2/8) to give [7a-(4-Cyano-benzyl)-3-(3,5-Dichlorophenyl)-2-oxo-2,3,5,6,7,7a-hexahydro-benzimidazol-3a-yl]-acetic acid ethyl ester (46.5 mg) as a white solid. 1H NMR (CDCl3): 7.55 (2H, d), 7.25 (2H, d), 7.1 (1H, m), 6.8 (2H, m), 5.0 (1H, m), 4.45 (1H, d), 4.2 (2H, q), 3.75 (1H, d), 3.05 (1H, d), 2.90 (1H, d), 2.5-2.1 (2H, m), 2.1-1.8 (4H, m), 1.25 (3H, t).

後処理

  1. waitAfter one night
  2. additionthe reaction mixture was poured on water
  3. extractionextracted with tBuOMe
  4. washThe organic layer was washed with water
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified on SiO2 chromatography (eluent EtOAc/cyclohexane—2/8)

出典と根拠

ORDレコード
ord-02b345ace84b4483aec5f737fb316f54
出典データセット
uspto-grants-2005_12
特許番号
US06974815B2

反応ノート

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