Ammonium Chloride → 1-[4-(tert-Butyldiphenylsilyloxymethyl)-1-ethoxymethyl-1H-imidazol-2-yl]-2,2-difluoroethanone

HRID 242377노트

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HRID 242377 반응식
[Si:1]([O:18][CH2:19][C:20]1[N:21]=[CH:22][N:23]([CH2:25][O:26][CH2:27][CH3:28])[CH:24]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CON(C)[C:37](=[O:41])[CH:38]([F:40])[F:39].[Cl-].[NH4+]>C1COCC1>[Si:1]([O:18][CH2:19][C:20]1[N:21]=[C:22]([C:37](=[O:41])[CH:38]([F:40])[F:39])[N:23]([CH2:25][O:26][CH2:27][CH3:28])[CH:24]=1)([C:14]([CH3:15])([CH3:16])[CH3:17])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 25517Ammonium ChlorideHCID 190237312,2-Difluoro-N-methoxy-N-methylacetamideHCID 710872724-(tert-Butyldiphenylsilyloxymethyl)-1-ethoxymethyl-1H-imidazoleHCID 178418339Butyllithium

생성물 1

HCID 892621971-[4-(tert-Butyldiphenylsilyloxymethyl)-1-ethoxymethyl-1H-imidazol-2-yl]-2,2-difluoroethanone수율 72.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-78 °C

실험 절차

4-(tert-Butyldiphenylsilyloxymethyl)-1-ethoxymethyl-1H-imidazole (2.00 g) was dissolved in THF (10 mL), and was cooled to −78° C. while stirring under an argon atmosphere. To the present solution was added dropwise n-butyl lithium (2.69 M hexane solution, 3.18 mL) slowly using a syringe, followed by stirring at the same temperature for 30 minutes. Then, N-methoxy-N-methyl difluoroacetamide (1.41 g) was added using a syringe, and stirring was continued for 17 hours while the temperature was raised to room temperature. A saturated aqueous ammonium chloride solution was added to the reaction solution to terminate the reaction, followed by extraction with ethyl acetate. The combined extract was washed with saturated brine, dried over anhydrous sodium sulfate, and subsequently the solvent was distilled off under reduced pressure. The resulting residue was purified by flash chromatography (ethyl acetate/hexane=0%→20%) using silica gel column (product name: SNAP Cartridge KP-Sil 50 g, manufactured by Biotage, Ltd.) to afford the title compound (1.74 g).

후처리

  1. stirringby stirring at the same temperature for 30 minutes
  2. stirringstirring
  3. temperaturewas raised to room temperature
  4. customto terminate
  5. customthe reaction
  6. extractionfollowed by extraction with ethyl acetate
  7. extractionThe combined extract
  8. washwas washed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. distillationsubsequently the solvent was distilled off under reduced pressure
  11. customThe resulting residue was purified by flash chromatography (ethyl acetate/hexane=0%→20%)

출처 및 근거

ORD 기록
ord-9fc02b938f834fa99e2d88cf86831c4a
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653126B2

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