2-Fluoro-4-iodoaniline → 6-Fluoro-2-[(2-fluoro-4-iodophenyl)amino]nicotinic acid

HRID 500521ノート

反応式

HRID 500521 の反応式
[F:1][C:2]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:3]=1[NH2:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.F[C:21]1[N:29]=[C:28]([F:30])[CH:27]=[CH:26][C:22]=1[C:23]([OH:25])=[O:24]>C1COCC1>[F:30][C:28]1[CH:27]=[CH:26][C:22]([C:23]([OH:25])=[O:24])=[C:21]([NH:4][C:3]2[CH:5]=[CH:6][C:7]([I:9])=[CH:8][C:2]=2[F:1])[N:29]=1

参加物

5

反応物 3

HCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium HexamethyldisilazideHCID 105830702,6-Difluoropyridine-3-carboxylic acid

生成物 1

HCID 248220326-Fluoro-2-[(2-fluoro-4-iodophenyl)amino]nicotinic acid

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To solution of 2-fluoro-4-iodoaniline (0.82 g, 3.46 mmol) in THF (10 mL) at −78° C. LiHMDS (6.00 mL, 6.60 mmol) was added. After stirring for 15 min, 2,6-difluoronicotinic acid (0.50 g, 3.14 mmol) was added to the mixture. The mixture was allowed to warm to room temperature until completion. The mixture was washed with NaOH (1N) and extracted with ether. The aqueous layer was acidified with concentrated HCl and back-extracted with ethyl acetate. The organic layer was concentrated to afford product. Second crop of product was obtained by purifying the THF/ether layer with silica gel chromatography. LC/MS [Method B: rt. 9.09 min, m/z 377 (M+1)].

後処理

  1. customat −78° C
  2. washThe mixture was washed with NaOH (1N)
  3. extractionextracted with ether
  4. extractionback-extracted with ethyl acetate
  5. concentrationThe organic layer was concentrated
  6. customto afford product
  7. customSecond crop of product was obtained
  8. customby purifying the THF/ether layer with silica gel chromatography
  9. customLC/MS [Method B: rt. 9.09 min, m/z 377 (M+1)]

出典と根拠

ORDレコード
ord-4b0c752778064010b9a094f9d9f66a7a
出典データセット
uspto-grants-2010_08
特許番号
US07772233B2

反応ノート

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