Aniline → 5-Chloro-2-[(N-phenylamino)acetamido]benzoic Acid

HRID 1490297Notes

Reaction equation

HRID 1490297 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:11][C:12](=[O:15])[CH2:13]Br)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[OH-].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:11][C:12](=[O:15])[CH2:13][NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]

Participants

5

Reactant 3

HCID 6115AnilineHCID 14797Potassium HydroxideHCID 107800225-Chloro-2-(bromoacetamido)benzoic Acid

Product 1

HCID 108283815-Chloro-2-[(N-phenylamino)acetamido]benzoic Acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-chloro-2-(bromoacetamido)benzoic acid from Example 41 (10 g, 0.03 mol), aniline (8 g, 7.8 mL, 250 mol %) and DMF (60 mL) was heated at 100°-110° C. for 4 h. The reaction mixture was poured into ice-water (200 mL) and the resulting solid product was solubilized by adding 5% KOH (40 mL). The mixture was extracted with CH2Cl2 (3×100 mL) and the aqueous layer was acidified with 5% HBr to pH=3 and extracted with EtOAc (3×200 mL). The EtOAc washings were dried (Na2SO4), filtered and concentrated to afford, after drying under vacuum, 7.8 g (75%) of the title compound as a white solid, mp 210°-212° C.; 1H NMR (DMSO-d6) δ 13.99 (s, 1H, NH), 11.96 (s, 1H, COOH), 8.75 (d, 1H, J=8), 7.87 (d, 1H, J=2.8), 7.68 (d, 1H, J=2.4), 7.65 (d, 1H, J=2.8), 7.10 (t, 2H, J=7.6), 6.61 (m, 4H), 3.84 (s, 2H); 13C NMR (DMSO-d6) δ 171.08, 167.81, 148.05, 139.36, 133.81, 130.25, 128.97, 126.20, 121.25, 117.77, 117.14, 112.45, 48.90; MS (EI, m/z) 304 (M+).

Workup

  1. extractionThe mixture was extracted with CH2Cl2 (3×100 mL)
  2. extractionextracted with EtOAc (3×200 mL)
  3. dry with materialThe EtOAc washings were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford
  7. dry with materialafter drying under vacuum, 7.8 g (75%) of the title compound as a white solid, mp 210°-212° C.

Sources & evidence

ORD record
ord-067a221d6b7a43db85a52c8838fa2f0b
Source dataset
uspto-grants-1997_10
Patent number
US05681958

Reaction notes

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