Iodoethane → HCID 67185128, 화합물

HRID 1843633노트

반응식

HRID 1843633 반응식
[CH2:1]([N:8]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([C:16]2[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)=[CH:19][NH:18][N:17]=2)[C:10]=1[F:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[CH2:37](I)[CH3:38]>C(Cl)Cl.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[CH2:28]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([C:16]2[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)=[CH:19][N:18]([CH2:37][CH3:38])[N:17]=2)[C:10]=1[F:27])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

참가 물질

7

반응물 3

HCID 6340IodoethaneHCID 14798Sodium HydroxideHCID 178505869HCID 178505869, 화합물

생성물 1

HCID 67185128HCID 67185128, 화합물수율 52%

시약·촉매·용매 3

HCID 74236Tetrabutylammonium Bromide촉매HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

Dibenzyl[2,4-difluoro-3-(4-pyridin-4-yl-1H-pyrazol-3-yl)-phenyl]-amine (prepared as described in Example 22) (4 g, 8.84 mmol) was suspended in DCM (44 mL) and 32% NaOH (44 mL) was added followed by tetrabutylammonium bromide (400 mg, 1.24 mmol, 0.14 eq). Neat ethyliodide (1.07 mL, 13.27 mmol, 1.5 eq) was then added and the biphasic mixture was vigorously stirred at room temperature for 1 h. By HPLC analysis at 254 nm the regioisomeric ratio was 55:45 in favour of the most polar N1-substituted pyrazole. The reaction mixture was then diluted with water (50 mL) and DCM (50 mL) and the two layers were separated. Aqueous phase was extracted with DCM (2×50 mL) and combined organic layers were washed with water (2×50 mL) and brine (50 mL), dried over Na2SO4 and evaporated to dryness. The two reagioisomers were separated by flash chromatography on silica gel (n-hexane/ethyl acetate 1:1) and the desired N1-ethylpyrazole was obtained as a white solid in 52% yield.

후처리

  1. customthe two layers were separated
  2. extractionAqueous phase was extracted with DCM (2×50 mL)
  3. washwere washed with water (2×50 mL) and brine (50 mL)
  4. dry with materialdried over Na2SO4
  5. customevaporated to dryness
  6. customThe two reagioisomers were separated by flash chromatography on silica gel (n-hexane/ethyl acetate 1:1)

출처 및 근거

ORD 기록
ord-e6c063344d5b42998b92e504966d8beb
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946250B2

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