Ammonium Chloride → 3-Amino-6-fluoro-2-phenylaminobenzoic acid methyl ester

HRID 242977Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:21])[C:4]1[C:9]([F:10])=[CH:8][CH:7]=[C:6]([N+:11]([O-])=O)[C:5]=1[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[NH4+].[Cl-]>CO.O.[Fe]>[CH3:1][O:2][C:3](=[O:21])[C:4]1[C:9]([F:10])=[CH:8][CH:7]=[C:6]([NH2:11])[C:5]=1[NH:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a mixture of 6-fluoro-3-nitro-2-phenylaminobenzoic acid methyl ester (2.1 g, 7.24 mmol) in a mixture of MeOH (50 mL) and water (15 mL) were added NH4Cl (2.23 g, 43.4 mmol) and iron powder (1.61 g, 28.9 mmol) and the reaction mixture heated at 90° C. for 3 h. After cooling to RT, the suspension was filtered through a pad of Celite® washing with additional MeOH. The filtrate was concentrated in vacuo to remove the organic solvent and the resulting aqueous residue extracted with EtOAc (×3). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo to afford the title compound as an orange oil which solidified on standing (2.0 g, quantitative). 1H NMR (CDCl3, 400 MHz): δ 7.23-7.18 (2H, m), 7.13 (1H, br s), 6.89-6.80 (3H, m), 6.69-6.64 (2H, m), 3.83 (3H, s)

Workup

temperatureAfter cooling to RT
filtrationthe suspension was filtered through a pad of Celite®
washwashing with additional MeOH
concentrationThe filtrate was concentrated in vacuo
customto remove the organic solvent
extractionthe resulting aqueous residue extracted with EtOAc (×3)
washThe combined organic fractions were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-82b5b164405841e49d10341f5c8cff80
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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