Hydrochloric Acid → N-(3-Aminophenyl)-2-chloro-4-fluorobenzamide

HRID 1591856Notes

Reaction equation

HRID 1591856 reaction equation
[Cl:1][C:2]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-])=O)[CH:8]=1)=[O:5].O.O.Cl[Sn]Cl.Cl.[OH-].[NH4+]>C(O)C>[NH2:13][C:9]1[CH:8]=[C:7]([NH:6][C:4](=[O:5])[C:3]2[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:2]=2[Cl:1])[CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 61436Stannous chloride dihydrateHCID 265746842-chloro-4-fluoro-N-(3-nitrophenyl)benzamide

Product 1

HCID 16775600N-(3-Aminophenyl)-2-chloro-4-fluorobenzamideYield 69%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

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. temperatureat reflux under a nitrogen atmosphere for 2 hr
  2. filtrationFilter through celite
  3. washwash with dichloromethane (2×15 mL)
  4. customseparate the filtrate
  5. extractionextract with dichloromethane (2×80 mL)
  6. dry with materialdry the combined organic layers over magnesium sulfate
  7. filtrationFilter
  8. concentrationconcentrate to dryness

Sources & evidence

ORD record
ord-ba1822fa271248da84f8144070e05191
Source dataset
uspto-grants-2007_11
Patent number
US07291632B2

Reaction notes

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