Phenylboronic Acid → (S)-2-(7-phenyl-1-oxo-1H-isoquinolin-2-yl)-butyric acid

HRID 1987882Notes

Reaction equation

HRID 1987882 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]([C@@H:13]([CH2:17][CH3:18])[C:14]([OH:16])=[O:15])[C:9]2=[O:12])=[CH:4][CH:3]=1.[C:19]1(B(O)O)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[F-].[K+]>C1COCC1.Cl.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>[C:19]1([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[CH:7][N:8]([C@@H:13]([CH2:17][CH3:18])[C:14]([OH:16])=[O:15])[C:9]3=[O:12])=[CH:4][CH:3]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

9

Reactant 3

HCID 66827Phenylboronic AcidHCID 522689Potassium FluorideHCID 11565197(S)-2-(7-chloro-1-oxo-1H-isoquinolin-2-yl)-butyric acid

Product 1

HCID 57725374(S)-2-(7-phenyl-1-oxo-1H-isoquinolin-2-yl)-butyric acidYield 66.1%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 27342152-(Di-tert-butylphosphino)biphenylCatalystHCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-2-(7-chloro-1-oxo-1H-isoquinolin-2-yl)-butyric acid (prepared as described in methods A-E) (200 mg) and phenyl boronic acid (276 mg) in THF (2 ml) was added palladium (II) acetate (1.7 mg), 2-(di-tert-butylphosphino)biphenyl (4.5 mg) and potassium fluoride (262 mg). The resulting mixture was heated at reflux for 18 hours, then cooled and diluted with 1M HCl (5 ml) and ethyl acetate (15 ml). The organic phase was separated and the aqueous extracted with ethyl acetate (2×15 ml). The combined organics were dried (magnesium sulfate), filtered and concentrated. The residue was purified through a plug of silica gel, then further purified by radial chromatography eluting with 1% acetic acid in ethyl acetate. This gave the subtitled product as a brown solid (153 mg, 66%). 1H NMR (400 MHZ, CDCl3) δ 1.00 (3H, t), 2.15 (1H, m), 2.40 (1H, m), 5.37 (1H, m), 6.70 (1H, d), 7.15 (1H, d), 7.45 (1H, m), 7.55 (2H, m), 7.68 (1H, m), 7.75 (2H, m), 7.99 (1H, d), 8.70 (1H, s) ppm.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 18 hours
  3. temperaturecooled
  4. customThe organic phase was separated
  5. extractionthe aqueous extracted with ethyl acetate (2×15 ml)
  6. dry with materialThe combined organics were dried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified through a plug of silica gel
  10. customfurther purified by radial chromatography
  11. washeluting with 1% acetic acid in ethyl acetate

Sources & evidence

ORD record
ord-de760536a530409ab90c7e133833c680
Source dataset
uspto-grants-2009_06
Patent number
US07553852B2

Reaction notes

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