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

HRID 1500691ノート

反応式

HRID 1500691 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-2007b69984774ad2a5d8cf865f92028b
出典データセット
uspto-grants-2015_12
特許番号
US09206174B2

反応ノート

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