Tributyl(4-fluorophenyl)stannane → 7-(4-Fluoro-phenyl)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester

HRID 1481157ノート

反応式

HRID 1481157 の反応式
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11](Br)[CH:10]=2)=[O:5])[CH3:2].[F:18][C:19]1[CH:24]=[CH:23][C:22]([Sn](CCCC)(CCCC)CCCC)=[CH:21][CH:20]=1>CN(C=O)C.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([C:22]1[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=1)[CH:10]=2)=[O:5])[CH3:2]

参加物

6

反応物 2

HCID 2737524Tributyl(4-fluorophenyl)stannaneHCID 89813095Ethyl 7-bromo-4-hydroxyisoquinoline-3-carboxylate

生成物 1

HCID 898130357-(4-Fluoro-phenyl)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester収率 55%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
120 °C

実験手順

7-Bromo-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester (250 mg, 0.8443 mmol) was dissolved in dry DMF and 4 Å molecular sieves were added to maintain dryness. 4-fluorophenyl-tri-n-butylstannane (392 mg, 1.013 mmol) and bis(triphenylphosphine)palladium(II) dichloride (71 mg, 0.1013 mmol) were added sequentially and the reaction heated to 120° C. in an oil bath. Upon completion, the reaction was cooled and diluted with ethyl acetate. The solution was washed with water then brine and the organic phase dried over sodium sulfate. The crude material was purified by medium pressure liquid chromatography (15 to 45% ethyl acetate in hexanes) to give the desired material in 55% yield as a thick yellow oil. 1H NMR (200 MHz, CDCl3): δ ppm=11.88 (s, 1H), 8.83 (s, 1H), 8.41 (d, 1H), 8.05 (s, 1H), 7.93 (d, 1H), 7.66 (m, 2H), 7.18 (t, 2H), 4.57 (q, 2H), 1.52 (t, 3H.)

後処理

  1. addition4 Å molecular sieves were added
  2. temperatureto maintain dryness
  3. temperatureUpon completion, the reaction was cooled
  4. washThe solution was washed with water
  5. dry with materialbrine and the organic phase dried over sodium sulfate
  6. customThe crude material was purified by medium pressure liquid chromatography (15 to 45% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-c1adf59fe0944e8c8de281fa0156e174
出典データセット
uspto-grants-2016_08
特許番号
US09409892B2

反応ノート

読み込み中…