2,6-Dichloro-5-fluoronicotinic acid → 6-Chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid

HRID 2063994노트

반응식

HRID 2063994 반응식
[F:1][C:2]1[CH:7]=[C:6]([Si:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[NH2:12].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl[C:24]1[N:32]=[C:31]([Cl:33])[C:30]([F:34])=[CH:29][C:25]=1[C:26]([OH:28])=[O:27]>C1COCC1>[Cl:33][C:31]1[C:30]([F:34])=[CH:29][C:25]([C:26]([OH:28])=[O:27])=[C:24]([NH:12][C:3]2[CH:4]=[CH:5][C:6]([Si:8]([CH3:9])([CH3:11])[CH3:10])=[CH:7][C:2]=2[F:1])[N:32]=1

참가 물질

5

반응물 3

HCID 27336592,6-Dichloro-5-fluoronicotinic acidHCID 2733832Lithium HexamethyldisilazideHCID 595965992-Fluoro-4-(trimethylsilyl)aniline

생성물 1

HCID 591401336-Chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid수율 49%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

To a cold (−78° C.) solution of 2-fluoro-4-trimethylsilanyl-phenylamine (19.2 g, 105 mmol) in anhydrous THF (50 mL) was added a solution of LHMDS (160 mL, 1 M in hexanes, 160 mmol) dropwise over 45 minutes under a nitrogen atmosphere. After 2 hours at −78° C., a solution of 2,6-dichloro-5-fluoro-nicotinic acid (10.5 g, 50 mmol) in anhydrous THF (30 mL) was added. The mixture was stirred at −78° C. for 1 hour then allowed to warm to ambient temperature. After 18 hours stirring at ambient temperature the reaction was quenched with water and adjusted to pH 2 by the addition of concentrated HCl. The solution was extracted with ethyl acetate and the organic layer was isolated, washed with water followed by brine, dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was triturated with methanol and filtered to afford the title compound as a yellow solid (8.7 g, 49%). LCMS (method B): RT=4.92 min, [M+H]+=357.

후처리

  1. temperatureto warm to ambient temperature
  2. stirringAfter 18 hours stirring at ambient temperature the reaction
  3. customwas quenched with water
  4. additionadjusted to pH 2 by the addition of concentrated HCl
  5. extractionThe solution was extracted with ethyl acetate
  6. customthe organic layer was isolated
  7. washwashed with water
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe resultant residue was triturated with methanol
  12. filtrationfiltered

출처 및 근거

ORD 기록
ord-06688221731b4785ab0e8f3a05ebf029
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288408B2

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