Lithium Hexamethyldisilazide → 2,6-difluoro-N-{1-[(2-methyl-5-nitrophenyl)methyl]-1H-pyrazol-3-yl}benzamide

HRID 1946345노트

반응식

HRID 1946345 반응식
[F:1][C:2]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][NH:9][N:8]=1)=[O:5].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:28][C:29]1[CH:34]=[C:33]([N+:35]([O-:37])=[O:36])[CH:32]=[CH:31][C:30]=1[CH3:38]>C1COCC1>[F:1][C:2]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][N:9]([CH2:28][C:29]2[CH:34]=[C:33]([N+:35]([O-:37])=[O:36])[CH:32]=[CH:31][C:30]=2[CH3:38])[N:8]=1)=[O:5]

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 509991612-(Bromomethyl)-1-methyl-4-nitrobenzeneHCID 178522346HCID 178522346, 화합물

생성물 1

HCID 595480222,6-difluoro-N-{1-[(2-methyl-5-nitrophenyl)methyl]-1H-pyrazol-3-yl}benzamide

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

To a solution of 2,6-difluoro-N-1H-pyrazol-3-ylbenzamide (for a preparation see Intermediate 9) (1.80 g, 8.07 mmol) in THF (30 ml) at ambient temperature under nitrogen was added 1.0 M lithium bis(trimethylsilyl)amide in THF (8 mL, 8.00 mmol) and stirred for 20 min. To the solution was added a solution of 2-(bromomethyl)-1-methyl-4-nitrobenzene (1.81 g, 7.87 mmol) in THF (20 ml) and stirred overnight. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (150 ml) and saturated aqueous sodium hydrogen carbonate (50 ml). The phases were separated and the aqueous phase washed with ethyl acetate (25 ml). The combined organic extracts were dried (MgSO4), filtered and the solvent removed in vacuo to leave a yellow oil (3.5 g). The residue was loaded in dichloromethane and purified on silica 100 g using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (2.1 g); LCMS (System 4) MH+=373, tRET=2.60 min.

후처리

  1. customat ambient temperature
  2. stirringstirred overnight
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between ethyl acetate (150 ml) and saturated aqueous sodium hydrogen carbonate (50 ml)
  5. customThe phases were separated
  6. washthe aqueous phase washed with ethyl acetate (25 ml)
  7. dry with materialThe combined organic extracts were dried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent removed in vacuo

출처 및 근거

ORD 기록
ord-71e5b297790a4d15bfea2391484f6cda
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399436B2

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