4-Chlorophenol → HCID 9906124, compound

HRID 992482Notes

Reaction equation

HRID 992482 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C([Mg]Br)C.[F:13][C:14]([F:27])([F:26])[C:15]1[CH:23]=[C:22]2[C:18]([C:19](=[O:25])[C:20](=[O:24])[NH:21]2)=[CH:17][CH:16]=1>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:19]2([OH:25])[C:18]3[C:22](=[CH:23][C:15]([C:14]([F:27])([F:13])[F:26])=[CH:16][CH:17]=3)[NH:21][C:20]2=[O:24])[CH:3]=1

Participants

5

Reactant 3

HCID 46844-ChlorophenolHCID 109876496-TrifluoromethylisatinHCID 178418443HCID 178418443, compound

Product 1

HCID 9906124HCID 9906124, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-chlorophenol (2.87 g, 22.3 mmol) in THF (30 mL) at 0° C., 1.0 M solution of ethyl magnesium bromide (22.3 mL, 22.3 mmol) in THF was added dropwise. The resulting white suspension was then concentrated to dryness and dissolved in CH2Cl2 (30 mL). Neat 6-(trifluoromethyl)isatin (4.0 g, 18.6 mmol) was then added at once. After stirring at room temperature for 4 hours, the reaction was quenched with 1N HCl solution. The organic layer was separated, washed with water and brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to provide a dark red oil which was purified by flash column chromatography (silica gel, 1:1 hexanes/EtOAc) to afford the title compound as an orange solid (5.48 g, 86% yield). 1H NMR (DMSO-d6): δ10.61 (s, 1H), 9.73 (s, 1H), 7.73(d, J=2.7 Hz, 1H), 7.15-7.21 (m, 2H), 7.03-7.07 (m, 2H), 6.81 (s, 1H), 6.61 (d, J=8.6 Hz, 1H).

Workup

  1. concentrationThe resulting white suspension was then concentrated to dryness
  2. dissolutiondissolved in CH2Cl2 (30 mL)
  3. customthe reaction was quenched with 1N HCl solution
  4. customThe organic layer was separated
  5. washwashed with water and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto provide a dark red oil which
  10. customwas purified by flash column chromatography (silica gel, 1:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-f98a5900b8854abbae80623f6d505771
Source dataset
uspto-grants-2002_10
Patent number
US06469042B1

Reaction notes

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