Triethylamine → Ethyl 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinate

HRID 241441ノート

反応式

HRID 241441 の反応式
Cl.Cl.[NH2:3][CH2:4][C:5]1[CH:6]=[C:7]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:8]([CH:11]([F:13])[F:12])=[N:9][CH:10]=1.C(N(CC)CC)C.[C:26](Cl)(=[O:30])[CH:27]([CH3:29])[CH3:28]>C(Cl)Cl>[F:12][CH:11]([F:13])[C:8]1[C:7]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:6][C:5]([CH2:4][NH:3][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])=[CH:10][N:9]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 86674201Ethyl 5-(aminomethyl)-2-(difluoromethyl)pyridine-3-carboxylate dihydrochloride

生成物 1

HCID 71059744Ethyl 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinate収率 77%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

Cool a mixture of ethyl 5-(aminomethyl)-2-(difluoromethyl)pyridine-3-carboxylate dihydrochloride (29.8 g, 111.8 mmol, 1.0 equiv), DCM (510 mL), and triethylamine (59.2 mL, 424.6 mmol, 3.8 equiv) to 0° C., then add a solution of isobutyryl chloride (15.3 mL, 145.3 mmol, 1.3 equiv) in DCM (23 mL) drop wise over 20 min. Stir overnight while allowing the mixture to warm to room temperature. Remove the solid precipitate by filtration, and rinse the filter with EtOAc (500 mL). Concentrate the filtrate under reduced pressure; filter the concentrate to remove the solids; and rinse the solids with EtOAc. Concentrate the filtrate under reduced pressure to give a yellow oil. Subject this crude material to silica gel chromatography eluting with a gradient of 40-90% EtOAc/hexanes gradient, to give the title compound as a light yellow crystalline solid (25.8 g, 77% yield). ES/MS (m/z) 301 (M+1).

後処理

  1. temperatureCool
  2. customRemove the solid precipitate
  3. filtrationby filtration
  4. washrinse the
  5. filtrationfilter with EtOAc (500 mL)
  6. concentrationConcentrate the filtrate under reduced pressure
  7. filtrationfilter the
  8. concentrationconcentrate
  9. customto remove the solids
  10. washand rinse the solids with EtOAc
  11. concentrationConcentrate the filtrate under reduced pressure
  12. customto give a yellow oil
  13. washeluting with a gradient of 40-90% EtOAc/hexanes gradient

出典と根拠

ORDレコード
ord-6da8dc3c62d340669ebf0dde28cb8623
出典データセット
uspto-grants-2014_02
特許番号
US08648200B2

反応ノート

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