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

HRID 1481157노트

반응식

HRID 1481157 반응식
[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]

참가 물질

6

반응물 2

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

생성물 1

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

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
120 °C

실험 절차

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.)

후처리

  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)

출처 및 근거

ORD 기록
ord-c1adf59fe0944e8c8de281fa0156e174
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409892B2

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