Methanol → HCID 18976225, compound

HRID 2393622Notes

Reaction equation

HRID 2393622 reaction equation
Cl.[NH2:2][CH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:4]1=[O:21].[C:22]1(=O)[O:27][C:25](=[O:26])[C:24]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:23]12.C(N(CC)CC)C.CO>ClC(Cl)C>[O:26]=[C:25]1[C:24]2[C:23](=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:22](=[O:27])[N:2]1[CH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:4]1=[O:21]

Participants

6

Reactant 4

HCID 887MethanolHCID 6811Phthalic Anhydride2×HCID 8471Triethylamine2×HCID 18976174HCID 18976174, compound

Product 1

HCID 18976225HCID 18976225, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

In one portion of 4.00 g (0.013 mole) of 3-amino-1-(4-fluorophenyl)-2,3-dihydro-5-methoxy-1H-indol-2-one hydrochloride in 80 ml of anhydrous dichloroethane, 2.69 g (0.0182 mole, 1.4 equivalent) of phthalic anhydride was added to a stirred suspension under argon atmosphere. 2 ml (0.0143 mole) of triethylamine was added dropwise to this mixture over 10 minutes. Then, after the whole was stirred at room temperature for 10 minutes, it was further refluxed over an oil bath overnight. Excessive phthalic anhydride was decomposed by adding a mixture of 2 ml of triethylamine and 2 ml of methanol and refluxing the resulting mixture for 20 minutes. The reaction mixture was concentrated under reduced pressure and then extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried. The residue obtained by removing ethyl acetate by evaporation was recrystallized from hexane-ethyl acetate to afford 4.50 g of 3-(1,2-dihydro-1,3-dioxoisoindol-2-yl)-1-(4-fluorophenyl)-2,3-dihydro-5-methoxy-1H-indol-2-one as colorless crystals. Melting point: 208.5° to 210.0° C., IR (Nujol) (cm-1): 1730, 1715, 1495, 1400, 1225, 1210, 750, 715, MS (DI, m/e): 402 (M+, base), 227, 184, 76.

Workup

  1. temperatureit was further refluxed over an oil bath overnight
  2. additionby adding
  3. temperaturerefluxing the resulting mixture for 20 minutes
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. extractionextracted with ethyl acetate
  6. washThe ethyl acetate layer was washed with water
  7. customdried
  8. customThe residue obtained
  9. customby removing ethyl acetate
  10. customby evaporation
  11. customwas recrystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-ee7d3540b85948c4baad758064ae89ba
Source dataset
uspto-grants-1998_09
Patent number
US05807883

Reaction notes

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