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

HRID 595031Notes

Reaction equation

HRID 595031 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.O.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 6422Trifluoroacetic acidHCID 5864187-FluoroisatinHCID 22242641Methanol--water (1/1)HCID 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 after addition was completed. The reaction mixture was judged complete by HPLC after 15 min. 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 A11A (18.84 g, 88%) as yellow solid: HPLC: RT=1.810 min (H2O/MeOH with TFA, CHROMOLITH® SpeedROD, 4.6×50 mm, gradient=4 min, wavelength=220 nm); MS(ES): m/z=226 [M+H+—H2O]; 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).

Workup

  1. additionafter 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 A11A (18.84 g, 88%) as yellow solid

Sources & evidence

ORD record
ord-c6f68f05c1b54bb9bdd87279f9cf5768
Source dataset
uspto-grants-2016_01
Patent number
US09242941B2

Reaction notes

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