3,5-Difluorobenzyl bromide → 3-(3,5-Difluorophenyl)-2-[2'-(3-methoxypropyl)-3-methylbiphenyl-4-yl]propanenitrile

HRID 2194925ノート

反応式

HRID 2194925 の反応式
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:19]#[N:20])=[C:14]([CH3:21])[CH:13]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[F:32][C:33]1[CH:34]=[C:35]([CH:38]=[C:39]([F:41])[CH:40]=1)[CH2:36]Br>C1COCC1.[NH4+].[Cl-]>[F:32][C:33]1[CH:34]=[C:35]([CH2:36][CH:18]([C:15]2[CH:16]=[CH:17][C:12]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[CH2:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:13][C:14]=2[CH3:21])[C:19]#[N:20])[CH:38]=[C:39]([F:41])[CH:40]=1

参加物

6

反応物 3

HCID 5188963,5-Difluorobenzyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 58083338[2'-(3-Methoxypropyl)-3-methylbiphenyl-4-yl]acetonitrile

生成物 1

HCID 674487153-(3,5-Difluorophenyl)-2-[2'-(3-methoxypropyl)-3-methylbiphenyl-4-yl]propanenitrile

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 25517Ammonium Chloride溶媒

反応条件

温度
-78 °C

実験手順

To a solution of [2′-(3-methoxypropyl)-3-methylbiphenyl-4-yl]acetonitrile (1.2 eq.) from step 1 in THF (0.02M) at −78° C. was added lithium hexamethyldisilazide (LiHMDS; 1.3 eq.). The reaction mixture was stirred 15 min at −78° C. To the resulting solution was cannulated a solution of 3,5-difluorobenzyl bromide (1 eq.) in THF (0.04M). The final mixture was allowed to warm slowly to room temperature and then stirred and extra 4 h. The resulting mixture was poured in saturated aqueous NH4Cl and extracted with EtOAc. The organic extract was dried over Na2SO4, filtered and concentrated. Purification by column chromatography on silica gel (Combi-Flash by ISCO), eluting with Hex/EtOAc (0 to 50% in 30 min) afforded the desired compound as a colorless oil.

後処理

  1. temperatureto warm slowly to room temperature
  2. stirringstirred and extra 4 h
  3. extractionextracted with EtOAc
  4. extractionThe organic extract
  5. dry with materialwas dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography on silica gel (Combi-Flash by ISCO)
  9. washeluting with Hex/EtOAc (0 to 50% in 30 min)

出典と根拠

ORDレコード
ord-a7e6c0f2639848618e79ddba11ff9445
出典データセット
uspto-grants-2012_12
特許番号
US08334308B2

反応ノート

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