Diisopropylamine → 2-methyl-3-[1-[4-[[2-(trimethylsilyl)ethyl]sulfonyl]phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine

HRID 1352999ノート

反応式

HRID 1352999 の反応式
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[C:19]([C:20]2[N:21]([C:29]3[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:31][CH:30]=3)[CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[N:24]=2)=[CH:18][CH:17]=[CH:16][N:15]=1.I[CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42]>C1COCC1>[CH3:13][C:14]1[C:19]([C:20]2[N:21]([C:29]3[CH:34]=[CH:33][C:32]([S:35]([CH2:38][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])(=[O:37])=[O:36])=[CH:31][CH:30]=3)[CH:22]=[C:23]([C:25]([F:27])([F:28])[F:26])[N:24]=2)=[CH:18][CH:17]=[CH:16][N:15]=1

参加物

6

反応物 4

HCID 7912DiisopropylamineHCID 77877(Iodomethyl)trimethylsilaneHCID 10786069Pyridine,2-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1h-imidazol-2-yl]-HCID 178418339Butyllithium

生成物 1

HCID 229977722-methyl-3-[1-[4-[[2-(trimethylsilyl)ethyl]sulfonyl]phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine収率 74%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a solution of diisopropylamine (0.7 mL, 0.005 mol) in 9 mL of dry THF was added butyllithium (BuLi) (2.83 mL of 1.62M solution in hexane, 4.6 mmol) at 0° C. The solution was stirred at this temperature for 5 minutes and cooled to −78° C. with a dry ice/isopropanol bath. A solution of 2-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine (Example 44) (1.46 g, 3.8 mmol) in 12 mL of dry THF was added over 10 minutes and the reaction mixture was stirred at −78° C. for 1 hour. (Iodomethyl)trimethylsilane (1.23 g, 57 mmol) was added dropwise and the reaction mixture was warmed to room temperature and was stirred overnight. The reaction was quenched with 50 mL of 1 N HCl and the aqueous phase was extracted with ethyl acetate (3×60 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude mixture was purified by chromatography on silica gel (ethyl acetate/hexane, 65:35) to give 1.30 g of 2-methyl-3-[1-[4-[[2-(trimethylsilyl)ethyl]sulfonyl]phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine as a white solid (74%): mp(DSC) 155–157° C. Anal. Calc'd. for C21H24F3N3O2SSi: C, 53.94; H, 5.17; N, 8.99; S, 6.86. Found: C, 53.77; H, 4.94; N, 8.75; S, 6.98.

後処理

  1. stirringthe reaction mixture was stirred at −78° C. for 1 hour
  2. temperaturethe reaction mixture was warmed to room temperature
  3. stirringwas stirred overnight
  4. customThe reaction was quenched with 50 mL of 1 N HCl
  5. extractionthe aqueous phase was extracted with ethyl acetate (3×60 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude mixture was purified by chromatography on silica gel (ethyl acetate/hexane, 65:35)

出典と根拠

ORDレコード
ord-0d81bb326c134a50b3bb501774c4eead
出典データセット
uspto-grants-2007_05
特許番号
US07220770B2

反応ノート

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