Tetrahydrofuran → (1-(tert-Butoxycarbonyl)-4-(4-fluorophenyl)piperidin-4-yl)methyl 6-chloro-2-oxo-1,3-bis((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-benzo[d]imidazole-4-carboxylate

HRID 913938ノート

反応式

HRID 913938 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]([O:14][CH2:15][C:16]2([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)=[O:13])[C:5]2[NH:9][C:8](=[O:10])[NH:7][C:6]=2[CH:11]=1.C1(N(C)C2CCCCC2)CCCCC1.Cl[CH2:51][O:52][CH2:53][CH2:54][Si:55]([CH3:58])([CH3:57])[CH3:56].[O:59]1[CH2:63][CH2:62]C[CH2:60]1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]([O:14][CH2:15][C:16]2([C:29]3[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[CH2:18][CH2:17]2)=[O:13])[C:5]2[N:9]([CH2:51][O:52][CH2:53][CH2:54][Si:55]([CH3:58])([CH3:57])[CH3:56])[C:8](=[O:10])[N:7]([CH2:60][O:59][CH2:63][CH2:62][Si:55]([CH3:57])([CH3:56])[CH3:54])[C:6]=2[CH:11]=1

参加物

5

反応物 4

HCID 8028TetrahydrofuranHCID 24210N-Methyl dicyclohexylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 57546031(1-(tert-butoxycarbonyl)-4-(4-fluorophenyl)piperidin-4-yl)methyl 6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-4-carboxylate

生成物 1

HCID 57546185(1-(tert-Butoxycarbonyl)-4-(4-fluorophenyl)piperidin-4-yl)methyl 6-chloro-2-oxo-1,3-bis((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-benzo[d]imidazole-4-carboxylate

実験手順

To a solution of (1-(tert-butoxycarbonyl)-4-(4-fluorophenyl)piperidin-4-yl)methyl 6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-4-carboxylate (0.5 g, 0.99 mmol) and N-cyclohexyl-N-methylcyclohexanamine (0.70 mL, 3.3 mmol) in tetrahydrofuran (6.5 mL) at 0° C. was added (2-(chloromethoxy)ethyl)trimethylsilane (0.56 mL, 3.2 mmol). After 5 min, the ice bath was removed and stirring continued at room temperature for 24 h. The reaction was allowed to stir overnight. The reaction was diluted with diethyl ether, washed with water, then 1M potassium bisulfate, then water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography (12%→25% ethyl acetate/n-hexane) gave 580 mg (76%) as an amorphous white foam solid. 1H-NMR (CDCl3, 500 MHz) δ 7.37 (dd, J=8.9, 5.2 Hz, 2H), 7.27 (d, J=2.1 Hz, 1H), 7.08 (m, 3H), 5.43 (s, 2H), 5.27 (s, 2H), 4.26 (s, 2H), 3.78 (m, 2H), 3.55 (t, J=8.1 Hz, 2H), 3.27 (t, J=8.1 Hz, 2H), 3.08 (m, 2H), 2.23 (m, 2H), 1.88 (m, 2H), 1.42 (s, 9H), 0.89 (t, J=8.2 Hz, 2H), 0.71 (t, J=8.1 Hz, 2H), −0.05 (s, 9H), −0.12 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 164.6, 161.7 (d, J=247 Hz), 154.9, 154.7, 137.1 (d, J=3.8 Hz), 131.3, 128.9 (d, J=7.7 Hz), 127.1, 125.4, 122.8, 116.9, 115.7 (d, J=20 Hz), 112.3, 79.7, 73.3, 71.9, 70.9, 66.5, 65.6, 40.6, 39.9, 32.2, 28.5, 17.8, 17.7, −1.3, ″1.4. Mass spec.: 786.00 (MNa)+.

後処理

  1. customthe ice bath was removed
  2. waitcontinued at room temperature for 24 h
  3. stirringto stir overnight
  4. additionThe reaction was diluted with diethyl ether
  5. washwashed with water
  6. dry with material1M potassium bisulfate, then water, then brine, dried over magnesium sulfate
  7. concentrationconcentrated
  8. customColumn chromatography (12%→25% ethyl acetate/n-hexane) gave 580 mg (76%) as an amorphous white foam solid

出典と根拠

ORDレコード
ord-868b434594154b55bf5ef1e4816d0a3d
出典データセット
uspto-grants-2011_09
特許番号
US08026257B2

反応ノート

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