Diisopropylamine → Ethyl 8-bromo-4-oxo-2-(3-(trifluoromethyl)phenyl)-1,4-dihydro-1,6-naphthyridine-3-carboxylate

HRID 520471ノート

反応式

HRID 520471 の反応式
C(NC(C)C)(C)C.[Li]CCCC.[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14].[Br:19][C:20]1[C:25]2[N:26]=[C:27]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=3)[O:28][C:29](=O)[C:24]=2[CH:23]=[N:22][CH:21]=1.[OH-].[Na+]>[Cl-].[Na+].O.C1COCC1>[Br:19][C:20]1[CH:21]=[N:22][CH:23]=[C:24]2[C:25]=1[NH:26][C:27]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:38])([F:40])[F:39])[CH:32]=1)=[C:14]([C:13]([O:16][CH2:17][CH3:18])=[O:15])[C:29]2=[O:28]

参加物

8

反応物 5

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 585528348-bromo-2-(3-(trifluoromethyl)phenyl)-4H-pyrido[4,3-d][1,3]oxazin-4-oneHCID 178418339Butyllithium

生成物 1

HCID 58552956Ethyl 8-bromo-4-oxo-2-(3-(trifluoromethyl)phenyl)-1,4-dihydro-1,6-naphthyridine-3-carboxylate収率 77.2%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
-78 °C

実験手順

A mixture of THF (15 mL) and diisopropylamine (1.40 mL, 10.0 mmol) was cooled to −78° C., and n-BuLi (4.0 mL, 2.5 M in hexanes, 10.0 mmol) was added. After stirring at −78° C. for 20 min, ethyl acetate (1.0 L, 10.2 mmol) was added and stirring was continued for 5 min. 8-bromo-2-(3-(trifluoromethyl)phenyl)-4H-pyrido[4,3-d][1,3]oxazin-4-one 47 (990 mg, 2.67 mmol) was added. After 1 h, the reaction mixture was gradually warmed to room temperature. 1N NaOH (15 mL) was added and the reaction mixture was stirred for 24 h. The mixture was poured into brine (50 mL), extracted with ethyl acetate (2×50 mL), dried (MgSO4), and concentrated in vacuo. The resulting solid was purified by MPLC to give 48 (910 mg, 77% yield).

後処理

  1. stirringstirring
  2. waitwas continued for 5 min
  3. waitAfter 1 h
  4. temperaturethe reaction mixture was gradually warmed to room temperature
  5. stirringthe reaction mixture was stirred for 24 h
  6. extractionextracted with ethyl acetate (2×50 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe resulting solid was purified by MPLC

出典と根拠

ORDレコード
ord-a10695db03d04960b1023d3de8286f7b
出典データセット
uspto-grants-2016_05
特許番号
US09326986B2

反応ノート

読み込み中…