Methanol → 7-Fluoro-1,3-dihydro-3-hydroxy-3-phenyl-2H-indol-2-one

HRID 1486445Notes

Reaction equation

HRID 1486445 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8](=[O:11])[C:7]2=[O:12].[C:13]1([Mg]Br)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CO.C(O)(C(F)(F)F)=O>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8](=[O:11])[C:7]2([OH:12])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 5864187-FluoroisatinHCID 178418255HCID 178418255, compound

Product 1

HCID 214394257-Fluoro-1,3-dihydro-3-hydroxy-3-phenyl-2H-indol-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 7-fluoroindoline-2,3-dione (12.22 g, 74 mmol) in THF (40 mL) at 0° C. was added phenylmagnesium bromide (148 mL, 148 mmol) dropwise. The reaction mixture was allowed to stir at room temperature for 15 min after the addition was completed. The reaction mixture was quenched with saturated NH4Cl and extracted with EtOAc. The combined extracts were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel chromatography (EtOAc/hexane) to afford Intermediate A-7A (18.84 g, 88%) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 10.92 (s, 1H), 7.37-7.25 (m, 5H), 7.19 (ddd, J=10.4, 8.1, 1.3 Hz, 1H), 7.04-6.92 (m, 2H); HPLC: RT=1.810 min (CHROMOLITH® SpeedROD column 4.6×50 mm, 10-90% aqueous methanol over 4 minutes containing 0.1% TFA, 4 mL/min, monitoring at 220 nm); MS(ES): m/z=599 [M+H−H2O]+.

Workup

  1. additionafter the addition
  2. customThe reaction mixture was quenched with saturated NH4Cl
  3. extractionextracted with EtOAc
  4. washThe combined extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (EtOAc/hexane)
  9. customto afford Intermediate A-7A (18.84 g, 88%) as a yellow solid

Sources & evidence

ORD record
ord-dd1457efc70b464782408d4235959261
Source dataset
uspto-grants-2016_08
Patent number
US09427442B2

Reaction notes

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