Dimethylformamide → 6-Chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

HRID 2063969ノート

反応式

HRID 2063969 の反応式
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Si:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][C:13]=2[F:22])[N:3]=1.[CH3:23]CN(C(C)C)C(C)C.CN(C=O)C.C(Cl)(=O)C(Cl)=O>ClCCl.CO>[CH3:23][O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([Cl:1])=[N:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([Si:18]([CH3:19])([CH3:21])[CH3:20])=[CH:14][C:13]=1[F:22]

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 81531Diisopropylethylamine2 回HCID 591401476-Chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)nicotinic acid

生成物 1

HCID 591401556-Chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

To a suspension of 6-chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid (33.7 g, 99.5 mmol) in dichloromethane (500 mL) at 0° C. was added DIPEA (17.1 mL, 99.5 mmol). The reaction mixture was stirred for 10 minutes, then DMF (2 mL) and oxalyl chloride (8.7 mL, 99.5 mmol) were added dropwise (CAUTION: EFFERVESCENCE). The reaction mixture was stirred at room temperature for 2 hours and then added dropwise to a solution of DIPEA (17.1 mL, 99.5 mmol) in MeOH (500 mL) at 0° C. over a 45 minutes period. The reaction mixture was stirred at room temperature for 18 hours before being concentrated in vacuo. The resultant residue was dissolved in ethyl acetate and washed with a saturated aqueous solution of sodium hydrogen carbonate, followed by water, then brine, dried (Na2SO4), filtered and evaporated in vacuo to afford the title compound as a brown foam which was used without purification into the next step (36.4 g). LCMS (method B) RT=5.35 min, M+H+=353.

後処理

  1. stirringThe reaction mixture was stirred at room temperature for 2 hours
  2. stirringThe reaction mixture was stirred at room temperature for 18 hours
  3. concentrationbefore being concentrated in vacuo
  4. dissolutionThe resultant residue was dissolved in ethyl acetate
  5. washwashed with a saturated aqueous solution of sodium hydrogen carbonate
  6. dry with materialbrine, dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo

出典と根拠

ORDレコード
ord-2cf7f0a62e7144319d485e326eb9c90e
出典データセット
uspto-grants-2012_10
特許番号
US08288408B2

反応ノート

読み込み中…