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

HRID 242377ノート

反応式

HRID 242377 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

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).

後処理

  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%)

出典と根拠

ORDレコード
ord-9fc02b938f834fa99e2d88cf86831c4a
出典データセット
uspto-grants-2014_02
特許番号
US08653126B2

反応ノート

読み込み中…