Sodium hydride → ethyl 3-((2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)methyl)benzoate

HRID 1183773ノート

反応式

HRID 1183773 の反応式
[H-].[Na+].[F:3][C:4]([F:23])([F:22])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16](=[O:21])[CH2:15][CH2:14]3)=[CH:7][CH:6]=1.Cl[CH2:25][C:26]1[CH:27]=[C:28]([CH:34]=[CH:35][CH:36]=1)[C:29]([O:31][CH2:32][CH3:33])=[O:30]>CN(C)C=O>[O:21]=[C:16]1[CH2:15][CH2:14][C:13]2[C:18](=[CH:19][CH:20]=[C:11]([C:8]3[CH:7]=[CH:6][C:5]([C:4]([F:3])([F:22])[F:23])=[CH:10][CH:9]=3)[CH:12]=2)[N:17]1[CH2:25][C:26]1[CH:27]=[C:28]([CH:34]=[CH:35][CH:36]=1)[C:29]([O:31][CH2:32][CH3:33])=[O:30]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 120009366-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-oneHCID 14812190Ethyl 3-(chloromethyl)benzoate

生成物 1

HCID 46206945ethyl 3-((2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)methyl)benzoate収率 77.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a mixture of 95% dry sodium hydride (18 mg, 0.75 mmol) in anhydrous N,N-dimethylfounamide (4 mL) at room temperature was added a solution of 6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one (90 mg, 0.31 mmol) (PT-010 made as in Example 1B, above) in anhydrous N,N-dimethylformamide (1 mL). The reaction mixture was stirred for 30 minutes under an atmosphere of dry N2, followed by addition of a solution of ethyl 3-(chloromethyl)benzoate (100 mg, 1.00 mmol) in N,N-dimethylformamide (1.0 mL). The reaction mixture was stirred at room temperature until most of the starting material was converted (checked by LCMS), then it was quenched by addition of methanol (5 mL) The reaction mixture was concentrated under a reduced pressure, diluted with ethyl acetate (50 mL), and the organic phase washed with 2N sodium carbonate (20 mL), 30% ammonium chloride (20 mL), brine (20 mL), dried over magnesium sulfate, and the solvent removed under reduced pressure. The residue was dissolved in N,N-dimethylformamide (3 mL) and subjected to reverse phase HPLC with a gradient of acetonitrile/water (2% to 98%) to afford ethyl 3-((2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)methyl)benzoate (compound no. 91) (108 mg, 0.24 mmol, 77%) (PT-094). LCMS mz 455.0 (M+H), 476.0 (M+Na), anal HPLC>95% in purity. 1H NMR (400 MHz; CDCl3) δ 7.94 (m, 2H); 7.64 (m, 4H); 7.41 (m, 3H); 7.30-7.37 (m, 1H); 6.92 (d, J=8.6 Hz, 1H); 5.27 (s, 2H); 4.37 (q, J=7.0 Hz, 2H); 3.08 (m, 2H), 2.86 (m, 2H); 1.39 (t, J=7.0 Hz, 3H).

後処理

  1. stirringThe reaction mixture was stirred at room temperature until most of the starting material
  2. customit was quenched by addition of methanol (5 mL) The reaction mixture
  3. concentrationwas concentrated under a reduced pressure
  4. additiondiluted with ethyl acetate (50 mL)
  5. washthe organic phase washed with 2N sodium carbonate (20 mL), 30% ammonium chloride (20 mL), brine (20 mL)
  6. dry with materialdried over magnesium sulfate
  7. customthe solvent removed under reduced pressure
  8. dissolutionThe residue was dissolved in N,N-dimethylformamide (3 mL)

出典と根拠

ORDレコード
ord-0a8e501440ce45d2a68a954831ed0ac4
出典データセット
uspto-grants-2014_03
特許番号
US08664379B2

反応ノート

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