4,9-Bis(ethyloxy)naphtho[2,3-c]furan-1,3-dione → Ethyl {4-[4,9-bis(ethyloxy)-1,3-dioxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-3-fluorophenyl}acetate

HRID 889487Notes

Reaction equation

HRID 889487 reaction equation
[CH2:1]([O:3][C:4]1[C:16]2[C:15](=O)[O:14][C:13](=[O:18])[C:12]=2[C:11]([O:19][CH2:20][CH3:21])=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[CH:9]2)[CH3:2].[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:25][C:24]=1[F:35]>C(O)(=O)C.CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:20]([O:19][C:11]1[C:12]2[C:13](=[O:18])[N:22]([C:23]3[CH:28]=[CH:27][C:26]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:25][C:24]=3[F:35])[C:15](=[O:14])[C:16]=2[C:4]([O:3][CH2:1][CH3:2])=[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=12)[CH3:21]

Participants

6

Reactant 2

HCID 207619774,9-Bis(ethyloxy)naphtho[2,3-c]furan-1,3-dioneHCID 59760056Ethyl 2-(4-amino-3-fluorophenyl)acetate

Product 1

HCID 58399552Ethyl {4-[4,9-bis(ethyloxy)-1,3-dioxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-3-fluorophenyl}acetateYield 69%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

4,9-Bis(ethyloxy)naphtho[2,3-c]furan-1,3-dione (0.100 g, 0.35 mmol) in acetic acid (5 ml) was treated with DMAP (0.013 g, 0.11 mmol) then ethyl (4-amino-3-fluorophenyl)acetate (0.138 g, 0.70 mmol) and heated to reflux (120° C.) under argon overnight. The reaction mixture was cooled to room temperature and the solvent evaporated to afford a brown/orange oil which was diluted in DCM and washed with saturated NaHCO3 and then 2N HCl. The organics were dried over MgSO4 and evaporated to a brown oil which was purified by chromatography on silica gel eluting with ethyl acetate (0-20%) in hexane over 30 minutes. The evaporated fractions were triturated with hexane to give the title compound as a solid (0.110 g, 0.24 mmol, 69%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe solvent evaporated
  3. customto afford a brown/orange oil which
  4. washwashed with saturated NaHCO3
  5. dry with materialThe organics were dried over MgSO4
  6. customevaporated to a brown oil which
  7. customwas purified by chromatography on silica gel eluting with ethyl acetate (0-20%) in hexane over 30 minutes
  8. customThe evaporated fractions were triturated with hexane

Sources & evidence

ORD record
ord-d175aadc46ef462986fb4eee63342038
Source dataset
uspto-grants-2012_08
Patent number
US08252833B2

Reaction notes

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