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

HRID 2194925노트

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HRID 2194925 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 25517Ammonium Chloride용매

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온도
-78 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-a7e6c0f2639848618e79ddba11ff9445
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08334308B2

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