Oxalyl chloride → 6-Chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

HRID 1500692ノート

反応式

HRID 1500692 の反応式
[Cl:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([Si:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][C:14]=2[F:23])[N:3]=1.[C:24](Cl)(=O)C(Cl)=O>ClCCl.CN(C=O)C>[CH3:24][O:7][C:6](=[O:8])[C:5]1[CH:9]=[C:10]([F:11])[C:2]([Cl:1])=[N:3][C:4]=1[NH:12][C:13]1[CH:18]=[CH:17][C:16]([Si:19]([CH3:20])([CH3:22])[CH3:21])=[CH:15][C:14]=1[F:23]

参加物

5

反応物 2

HCID 65578Oxalyl chlorideHCID 591401336-Chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid

生成物 1

HCID 591401696-Chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester収率 92.4%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To a suspension of 6-chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid (7.6 g, 21.3 mmol) in dichloromethane (100 mL) and DMF (1 mL) was added oxalyl chloride (9.1 mL, 106.4 mmol) dropwise over 20 minutes. The reaction mixture was stirred at reflux for 18 hours and then concentrated in vacuo and the residue azeotroped with toluene. The resultant residue was taken up in cold (0° C.) methanol (100 mL). The resultant solution was heated at reflux for 1 hour, then cooled to room temperature and filtered. The precipitate was washed with cold methanol and dried under vacuum at 45° C. to give the title compound as a yellow solid (7.3 g, 92%). LCMS (method B): RT=5.38 min, [M+H]+=371.

後処理

  1. temperatureat reflux for 18 hours
  2. concentrationconcentrated in vacuo
  3. customthe residue azeotroped with toluene
  4. customwas taken up in cold (0° C.) methanol (100 mL)
  5. temperatureThe resultant solution was heated
  6. temperatureat reflux for 1 hour
  7. filtrationfiltered
  8. washThe precipitate was washed with cold methanol
  9. customdried under vacuum at 45° C.

出典と根拠

ORDレコード
ord-afda34a947624489a3640730663a00d7
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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