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

HRID 1481157Notes

Reaction equation

HRID 1481157 reaction equation
[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]

Participants

6

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

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.)

Workup

  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)

Sources & evidence

ORD record
ord-c1adf59fe0944e8c8de281fa0156e174
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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