2-Chloro-4-nitrobenzoic acid → HCID 10853940, compound

HRID 355942Notes

Reaction equation

HRID 355942 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.S(Cl)(Cl)=O.[NH:18]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[CH2:22][CH2:21][CH2:20][CH2:19]1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([N:18]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[CH2:22][CH2:21][CH2:20][CH2:19]1)=[O:6]

Participants

6

Reactant 4

HCID 74482-Chloro-4-nitrobenzoic acidHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 5765032,3,4,5-tetrahydro-1H-1-benzazepine

Product 1

HCID 10853940HCID 10853940, compoundYield 94.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 42.6 g (0.211 mol) of 2-chloro-4-nitrobenzoic acid is reacted with 420 ml of thionyl chloride (refluxed for 3 hours and the excess thionyl chloride removed). Toluene is added several times and the solvent removed. The residue is dissolved in 400 ml of CH2Cl2 and added dropwise to a cold (ice bath) solution of 28.2 g (0.192 mol) of 1,2,3,4-tetra-hydro-5H-1-benzazepine and 29.4 ml of triethylamine in 320 ml of dichloromethane. The mixture is stirred at room temperature overnight and is washed with H2O, 10% HCl and 10% NaHCO3. Activated carbon is added to the organic layer and the mixture is filtered through a layer of MgSO4. The solvent is removed under vacuum and the residue chromatographed on silica gel (in two batches) with ethyl acetate-CH2Cl2 (5:95) as eluent. The fractions containing product are combined and the solvent removed. The residue is dissolved in ethyl acetate and the solvent removed (foams). The residue is heated with hexane to give a solid (lumps broken up) and the mixture is filtered. The solid is washed with hexane and dried to give 59.9 g of 1,2,3,4-tetrahydro-1-(2-chloro-4-nitrobenzoyl)-5H-l-benzazepine as off-white crystals, m.p. 112°-114° C., mass spectrum (CI) 321 (MH+)

Workup

  1. temperaturerefluxed for 3 hours
  2. customthe excess thionyl chloride removed)
  3. additionToluene is added several times
  4. customthe solvent removed
  5. dissolutionThe residue is dissolved in 400 ml of CH2Cl2
  6. washis washed with H2O, 10% HCl and 10% NaHCO3
  7. additionActivated carbon is added to the organic layer
  8. filtrationthe mixture is filtered through a layer of MgSO4
  9. customThe solvent is removed under vacuum
  10. customthe residue chromatographed on silica gel (in two batches) with ethyl acetate-CH2Cl2 (5:95) as eluent
  11. additionThe fractions containing product
  12. customthe solvent removed
  13. dissolutionThe residue is dissolved in ethyl acetate
  14. customthe solvent removed (foams)
  15. temperatureThe residue is heated with hexane
  16. customto give a solid (lumps broken up)
  17. filtrationthe mixture is filtered
  18. washThe solid is washed with hexane
  19. customdried

Sources & evidence

ORD record
ord-7d0da959aaa046da8008fe50c813468e
Source dataset
uspto-grants-1998_11
Patent number
US05834461

Reaction notes

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