2-Fluoroaniline → 5-Bromo-3,4-difluoro-2-((2-fluorophenyl)amino)benzoic acid

HRID 558194ノート

反応式

HRID 558194 の反応式
[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Br:19][C:20]1[C:21]([F:31])=[C:22]([F:30])[C:23](F)=[C:24]([CH:28]=1)[C:25]([OH:27])=[O:26]>C1COCC1>[Br:19][C:20]1[C:21]([F:31])=[C:22]([F:30])[C:23]([NH:4][C:3]2[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=2[F:1])=[C:24]([CH:28]=1)[C:25]([OH:27])=[O:26]

参加物

5

反応物 3

HCID 95842-FluoroanilineHCID 2733832Lithium HexamethyldisilazideHCID 111186375-Bromo-2,3,4-trifluorobenzoic acid

生成物 1

HCID 595193885-Bromo-3,4-difluoro-2-((2-fluorophenyl)amino)benzoic acid収率 57.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of 2-fluoroaniline (4.27 ml, 44.3 mmol) in THF (30 ml) at −78° C. was added LiHMDS (66.6 ml, 1 M in THF, 66.6 mmol) dropwise. The reaction mixture was stirred for 10 min and a solution of 5-bromo-2,3,4-trifluorobenzoic acid (5.63 g, 22.2 mmol) in THF (40 ml) was added to the mixture. The reaction was slowly warmed to room temperature and stirred at this temperature for 4 h. The mixture was concentrated, quenched with 10% HCl solution (70 ml), and extracted with EtOAc (2×200 ml). The combined organic solution was dried over MgSO4 and concentrated to dryness. Purification by trituration with boiling CH2Cl2 gave 4.40 g (57%) of 5-bromo-3,4-difluoro-2-(2-fluorophenylamino)benzoic acid as a yellow solid.

後処理

  1. stirringstirred at this temperature for 4 h
  2. concentrationThe mixture was concentrated
  3. customquenched with 10% HCl solution (70 ml)
  4. extractionextracted with EtOAc (2×200 ml)
  5. dry with materialThe combined organic solution was dried over MgSO4
  6. concentrationconcentrated to dryness
  7. customPurification by trituration with boiling CH2Cl2

出典と根拠

ORDレコード
ord-3bdeb21ec0a74b539521ee25cb34289d
出典データセット
uspto-grants-2011_11
特許番号
US08063049B2

反応ノート

読み込み中…