Isobutyryl chloride → Ethyl 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinate

HRID 1469796ノート

反応式

HRID 1469796 の反応式
C(O[C:6]([NH:8][CH2:9][C:10]1[CH:11]=[N:12][C:13]([CH:21]([F:23])[F:22])=[C:14]([CH:20]=1)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:7])(C)(C)C.CCN(C(C)C)[CH:27]([CH3:29])[CH3:28].C(Cl)(=O)C(C)C>Cl.CCO.CCOC(C)=O>[F:23][CH:21]([F:22])[C:13]1[N:12]=[CH:11][C:10]([CH2:9][NH:8][C:6](=[O:7])[CH:27]([CH3:29])[CH3:28])=[CH:20][C:14]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16]

参加物

7

反応物 3

HCID 62325Isobutyryl chlorideHCID 81531DiisopropylethylamineHCID 71059899Ethyl 5-(((tert-butoxycarbonyl)amino)methyl)-2-(difluoromethyl)nicotinate

生成物 1

HCID 71059744Ethyl 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinate収率 44.1%

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid溶媒HCID 702Ethanol溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of ethyl 5-(((tert-butoxycarbonyl)amino)methyl)-2-(difluoromethyl)nicotinate (500 mg, 1.51 mmol) in HCl in EtOH (2 mL) was stirred at rt for 2 h. The reaction mixture was concentrated and the concentrate was dissolved in DMF (2 mL). The solution was treated with DIPEA (464 mg, 3.60 mmol) and isobutyryl chloride (115 mg, 1.08 mmol) at rt. The reaction mixture was stirred for 2 h before it was diluted with EtOAc and was washed with H2O and brine. The organic layer was separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 200 mg of the title product. 1H NMR (300 MHz, DMSO d6): δ 8.75 (s, 1H), 8.48 (t, 1H), 8.14 (s, 1H), 7.59-7.24 (t, J=54 Hz, 1H), 4.39-4.32 (m, 4H), 2.44 (m, 1H), 1.35-1.29 (t, J=6.9 Hz, 3H), 1.04-1.02 (d, J=6.9 Hz, 6H); MS [M+H]+: 301.36.

後処理

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe concentrate was dissolved in DMF (2 mL)
  3. washwas washed with H2O and brine
  4. customThe organic layer was separated
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography

出典と根拠

ORDレコード
ord-0db722cccb0445588862f4315928c95e
出典データセット
uspto-grants-2015_04
特許番号
US09006257B2

反応ノート

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