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

HRID 889501Notes

Reaction equation

HRID 889501 reaction equation
[Na+].[CH2:2]([O:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([O:15][CH2:16][CH3:17])=[C:7]([C:18]([O-])=[O:19])[C:6]=1[C:21]([O-])=[O:22])[CH3:3].[Na+].[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[C:28]([F:38])[CH:27]=1>C(O)(=O)C.O>[CH2:16]([O:15][C:8]1[C:7]2[C:18](=[O:19])[N:25]([C:26]3[CH:31]=[CH:30][C:29]([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[C:28]([F:38])[CH:27]=3)[C:21](=[O:22])[C:6]=2[C:5]([O:4][CH2:2][CH3:3])=[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=12)[CH3:17]

Participants

5

Reactant 2

HCID 15840528Ethyl 2-(4-amino-2-fluorophenyl)acetateHCID 58399579Disodium;1,4-diethoxynaphthalene-2,3-dicarboxylate

Product 1

HCID 58399553Ethyl {4-[4,9-bis(ethyloxy)-1,3-dioxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-2-fluorophenyl}acetateYield 84%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

A mixture of 1,4-bis(ethyloxy)-2,3-naphthalenedicarboxylic acid sodium salt (526 g, 1.51 mol) and ethyl (4-amino-2-fluorophenyl)acetate (539 g, 2.73 mol) in glacial acetic acid (5100 mL) was heated to reflux for 6 hours, with reaction progress monitored by 1H-nmr spectroscopy. The reaction mixture was allowed to cool to room temperature, stirred for 18 hours, diluted with water (14 L) and stirred for a further 30 minutes. The product was isolated by filtration, washed with water (5 L) and dried in a vacuum oven at 60° C. to give the desired product as an off-white solid (587 g, 84% yield).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 6 hours, with reaction progress
  3. stirringstirred for a further 30 minutes
  4. customThe product was isolated by filtration
  5. washwashed with water (5 L)
  6. customdried in a vacuum oven at 60° C.

Sources & evidence

ORD record
ord-29c428d91c1c44a7a4449fcfa4481ff6
Source dataset
uspto-grants-2012_08
Patent number
US08252833B2

Reaction notes

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