Methyl iodide → HCID 58968731、化合物

HRID 2075088ノート

反応式

HRID 2075088 の反応式
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[C:25]([CH:28]1[CH2:31][CH2:30][CH2:29]1)([OH:27])[CH3:26])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[H-].[Na+].I[CH3:44]>O1CCCC1>[CH:28]1([C:25]([C:16]2[CH:17]=[CH:18][C:19]([C:21]([F:24])([F:23])[F:22])=[CH:20][C:15]=2[CH2:14][N:7]([CH2:6][C:5]2[CH:4]=[C:3]([C:2]([F:1])([F:39])[F:40])[CH:34]=[C:33]([C:35]([F:36])([F:37])[F:38])[CH:32]=2)[C:8]2[N:9]=[N:10][N:11]([CH3:13])[N:12]=2)([O:27][CH3:44])[CH3:26])[CH2:31][CH2:30][CH2:29]1

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58968647HCID 58968647、化合物

生成物 1

HCID 58968731HCID 58968731、化合物収率 80%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 1-(2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)-1-cyclobutylethanol (22 mg; 0.038 mmol) in tetrahydrofuran (1.5 mL) was added sodium hydride (10 mg; 0.25 mmol; 60% dispersion in mineral oil). The reaction was stirred for 10 minutes. Iodomethane (0.05 mL; 0.80 mmol) was added. The reaction was stirred at room temperature for 16 hours. The reaction was quenched with water. The mixture was diluted with ethyl acetate and filtered over sodium sulfate and silica get column. After being concentrated under reduced pressure, the residue was taken up in ethyl acetate and washed with water (2×) and brine. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified over a 4 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 10-50% ethyl acetate in hexanes) to give 18 mg (80% yield) of the title compound as a colorless gum. MS (ES+): Calc: 595.5, Found: 596.5 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 7.78 (s, 1H), 7.73 (s, 2H), 7.45 (d, J=8.3 Hz, 1H), 7.43 (s, 1H), 7.3 (d, J=8.3 Hz, 1H), 5.09 (s, 2H), 4.8 (q, J=16.18 Hz, 2H), 4.2 (s, 3H), 3.04 (s, 3H), 2.83 (m, 1H) 1.99 (m, 1H), 1.89-1.6 (m, 6H), 1.59 (s, 3H).

後処理

  1. stirringThe reaction was stirred at room temperature for 16 hours
  2. customThe reaction was quenched with water
  3. additionThe mixture was diluted with ethyl acetate
  4. filtrationfiltered over sodium sulfate and silica
  5. customget column
  6. concentrationAfter being concentrated under reduced pressure
  7. washwashed with water (2×) and brine
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified over a 4 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 10-50% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-3e364ffe696e4f88914c23dc5181b1ce
出典データセット
uspto-grants-2011_04
特許番号
US07919506B2

反応ノート

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