5-Bromoisatin → HCID 5297654, compound

HRID 1052967Notes

Reaction equation

HRID 1052967 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[O:12].[F:13][C:14]1[CH:19]=[CH:18][C:17]([Mg]Br)=[CH:16][CH:15]=1>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2([C:17]1[CH:18]=[CH:19][C:14]([F:13])=[CH:15][CH:16]=1)[OH:12]

Participants

5

Reactant 2

HCID 68895-BromoisatinHCID 178418676HCID 178418676, compound

Product 1

HCID 5297654HCID 5297654, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-bromoindoline-2,3-dione (120 g, 530 mmol, 1.0 eq) in THF (1 L) was added dropwise (4-fluorophenyl)magnesium bromide in THF (0.8 M, 1.6 L, 1280 mmol, 2.4 eq) at 0° C.˜15° C., the mixture was stirred for overnight at room temperature. Then mixture was cooled to 0° C., quenched with H2O (20 mL), concentrated to give crude product, which was dissolved in EtOAc (2 L), washed with 1N HCl.aq (2 L), brine (1 L×2), dried over Na2SO4, the organic phase was concentrated to give crude product. Then the crude product was stirred in PE, filtered to obtained yellow solid, and dried in air to give 136 g (yield 80%) product, which was used to the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δH 10.58 (s, 1H), 7.44-7.46 (dd, 1H, J1=8.4 Hz, 2.0 Hz), 7.28-7.32 (m, 2H), 7.22-7.25 (m, 1H), 7.14-7.18 (t, 2H, J=8.8 Hz), 6.87-6.89 (d, 1H, J=8.4 Hz), 6.84 (s, 1H). MS (ESI) [M+1-18]+ 304, 306.

Workup

  1. temperatureThen mixture was cooled to 0° C.
  2. customquenched with H2O (20 mL)
  3. concentrationconcentrated
  4. customto give crude product, which
  5. washwashed with 1N HCl
  6. dry with materialaq (2 L), brine (1 L×2), dried over Na2SO4
  7. concentrationthe organic phase was concentrated
  8. customto give crude product
  9. filtrationfiltered
  10. customto obtained yellow solid
  11. customdried in air

Sources & evidence

ORD record
ord-62af09358ef04ceb90413738c0182ff6
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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