Ethyl 2-chloroacetoacetate → Ethyl 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate

HRID 2275754ノート

反応式

HRID 2275754 の反応式
[F:1][C:2]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:3]=1[CH2:4][O:5][C:6]1[C:7]([NH2:12])=[N:8][CH:9]=[CH:10][CH:11]=1.Cl[CH:19]([C:25]([CH3:27])=O)[C:20]([O:22][CH2:23][CH3:24])=[O:21]>C(O)C>[F:1][C:2]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:25]([CH3:27])[N:12]=2)[CH:9]=[CH:10][CH:11]=1

参加物

4

反応物 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 102634983-(2,6-Difluoro-benzyloxy)-pyridin-2-ylamine

生成物 1

HCID 86717871Ethyl 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate収率 41%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

170 g of 3-[(2,6-difluorobenzyl)oxy]pyridine-2-amine (Example 1A; 719 mmol, 1 equivalent) were initially charged in 3800 ml of ethanol, and 151 g of powdered molecular sieve 3 Å and 623 g of ethyl 2-chloroacetoacetate (3.6 mol, 5 equivalents) were added. The reaction mixture was heated at reflux for 24 h and then filtered off through silica gel and concentrated under reduced pressure. The mixture was kept at RT for 48 h, and the solid formed was filtered off. The solid was then stirred three times with a little isopropanol and then filtered off and washed with diethyl ether. This gave 60.8 g (23% of theory) of the title compound. The combined filtrates of the filtration steps were concentrated and the residue was chromatographed on silica gel using cyclohexane/diethyl ether as mobile phase. This gave a further 46.5 g (18% of theory; total yield: 41% of theory) of the title compound.

後処理

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 24 h
  3. filtrationfiltered off through silica gel
  4. concentrationconcentrated under reduced pressure
  5. customthe solid formed
  6. filtrationwas filtered off
  7. filtrationfiltered off
  8. washwashed with diethyl ether
  9. filtrationThe combined filtrates of the filtration steps
  10. concentrationwere concentrated
  11. customthe residue was chromatographed on silica gel

出典と根拠

ORDレコード
ord-82901139c5ee4079bef7d647350e0011
出典データセット
uspto-grants-2015_09
特許番号
US09126998B2

反応ノート

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