Pyridine → 2-chloro-4-fluoro-N-(3-nitrophenyl)benzamide

HRID 1716878Notes

Reaction equation

HRID 1716878 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7])([O-:3])=[O:2].N1C=CC=CC=1.[Cl:17][C:18]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:19]=1[C:20](Cl)=[O:21]>ClCCl>[Cl:17][C:18]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:19]=1[C:20]([NH:7][C:6]1[CH:8]=[CH:9][CH:10]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)=[O:21]

Participants

5

Reactant 3

HCID 1049PyridineHCID 74233-NitroanilineHCID 27365462-Chloro-4-fluorobenzoyl chloride

Product 1

HCID 265746842-chloro-4-fluoro-N-(3-nitrophenyl)benzamideYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Combine 3-nitroaniline (3.0 g, 21.7 mmol), dichloromethane (100 mL), pyridine (2.11 mL, 26.0 mmol) and 2-chloro-4-fluorobenzoyl chloride (3.07 mL, 23.9 mmol). Stir at room temperature overnight. Filter the white precipitate, rinse with ether (2×10 mL), and dry under vacuum to provide 2-chloro-4-fluoro-N-(3-nitrophenyl)benzamide (4.92 g, 77%). Combine the 2-chloro-4-fluoro-N-(3-nitrophenyl)benzamide (4.92 g, 16.7 mmol) with ethanol (150 mL), SnCl2-2H2O (18.9 g, 83.6 mmol) and concentrated hydrochloric acid (8.24 mL, 83.6 mmol). Stir at reflux under a nitrogen atmosphere for 2 hr. Neutralize with ammonium hydroxide (15 mL). Filter through Celite®, wash with dichloromethane (2×15 mL), separate the filtrate, extract with dichloromethane (2×80 mL), and dry the combined organic layers over magnesium sulfate. Filter and concentrate to dryness to provide the title intermediate as an off-white solid (3.04 g, 69%): mass spectrum (ion spray): m/z=265.0 (M+1); 1H NMR (DMSO-d6): 10.16 (bs, N—H), 7.60 (dd, J=6.2 Hz, 8.6 Hz, 1H), 7.54 (dd, J=2.5 Hz, 9.0 Hz, 1H), 7.30 (td, J=2.5 Hz, 8.5 Hz, 1H), 7.04 (t, J=2.0 Hz, 1H), 6.93 (t, J=8.0 Hz, 1H), 6.74 (bd, J=7.9 Hz, 1H), 6.29 (dd, J=2.2 Hz, 7.9 Hz, 1H), 5.10 (bs, 2H).

Workup

  1. filtrationFilter the white precipitate
  2. washrinse with ether (2×10 mL)
  3. customdry under vacuum

Sources & evidence

ORD record
ord-4a91c0aee7194a84a12802961655e1af
Source dataset
uspto-grants-2010_09
Patent number
US07803813B2

Reaction notes

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