Nitric Acid → N-(4-chloro-2-fluoro-5-nitrophenyl)acetamide

HRID 1107247Notes

Reaction equation

HRID 1107247 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[C:4]([F:12])[CH:3]=1.[N+:13]([O-])([OH:15])=[O:14]>S(=O)(=O)(O)O.C(OCC)(=O)C>[Cl:1][C:2]1[C:7]([N+:13]([O-:15])=[O:14])=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[C:4]([F:12])[CH:3]=1

Participants

5

Reactant 2

HCID 944Nitric AcidHCID 8531744'-Chloro-2'-fluoroacetanilide

Product 1

HCID 13563753N-(4-chloro-2-fluoro-5-nitrophenyl)acetamideYield 87.6%

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of N-(4-chloro-2-fluorophenyl)acetamide (180.6 g, 0.96 mol) in concentrated sulfuric acid (1L) was added a mixture of 175 mL of concentrated HNO3 and 175 mL of concentrated sulfuric acid at 0 to 5° C. in 1.5 h. After the addition was finished, the reaction mixture was stirred for another 0.5 h. The solution was poured into 5 L of ice water. After the product precipitated, it was isolated by filtration and then was dissolved in 2.5 L of ethyl acetate. After separation of the water layer, the organic layer was dried over sodium sulfate and then the solvent was evaporated. The crude product was triturated in diisopropyl ether (1.5 L), isolated by filtration, and dried under reduced pressure to afford the title compound of Step A (196.2 g, 87.6%) melting at 145-146° C. 1H NMR (Me2SO-d6) δ 10.3-10.2 (s, 1H), 8.9 (d, 1H), 7.9-7.8 (d, 2.2-2.1 (s, 3H).

Workup

  1. additionAfter the addition
  2. customAfter the product precipitated
  3. customit was isolated by filtration
  4. customAfter separation of the water layer
  5. dry with materialthe organic layer was dried over sodium sulfate
  6. customthe solvent was evaporated
  7. customThe crude product was triturated in diisopropyl ether (1.5 L)
  8. customisolated by filtration
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-33ca866d9c8349c891489728353ddb43
Source dataset
uspto-grants-2000_05
Patent number
US06060432

Reaction notes

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