Dichloromethane → HCID 14004019, compound

HRID 1252121Notes

Reaction equation

HRID 1252121 reaction equation
[NH:1]1[CH2:10][CH2:9][CH2:8][C:7]2[N:6]=[CH:5][C:4]3[CH:11]=[CH:12][CH:13]=[CH:14][C:3]=3[C:2]1=2.[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH2:22][C:23](Cl)=[O:24].ClCCl>CCOCC>[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH2:22][C:23]([N:1]1[CH2:10][CH2:9][CH2:8][C:7]2[N:6]=[CH:5][C:4]3[CH:11]=[CH:12][CH:13]=[CH:14][C:3]=3[C:2]1=2)=[O:24]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 182669Acetyl chloride, 2-(2-chlorophenyl)-HCID 138234741,2,3,4-Tetrahydrobenzo[c]-1,5-naphthyridine

Product 1

HCID 14004019HCID 14004019, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Powdered 1,2,3,4-tetrahydrobenzo[c]-1,5-naphthyridine (8.29 g) was added to ice cold, stirred 2-chlorophenylacetyl chloride (30 ml) without external cooling. A thick suspension of crystalline material formed and a mild exothermic reaction was observed. After stirring overnight at room temperature the suspension was gradually diluted with anhydrous ether to give a tacky solid which formed a gummy mass. On continued stirring the material solidified and disintegrated to give a suspension. The material was isolated by vacuum filtration and washed well with ether. A solution of the filter cake and water (300 ml) was basified with 10% sodium hydroxide solution and extracted with dichloromethane (2×250 ml). The combined turbid organic phase was washed once with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to an oil. A solution of the oil and toluene (150 ml) was concentrated to remove any residual moisture, whereupon the material solidified. Thin layer chromatographic analysis (silica gel, ethyl acetate) indicated the presence of 40-50% starting material. A solution of the solid in dichloromethane (200 ml) was added to stirred, ice-cold 2-chlorophenylacetyl chloride (27 ml) without external cooling. After three hours, the solution was concentrated to reduce the reaction volume, whereupon a suspension formed. Sufficient dichloromethane (200 ml) was added to afford a solution which was allowed to stand for 48 hours at room temperature. The solution was concentrated to remove most of the dichloromethane and the residual oil was treated with excess ethereal hydrogen chloride and diluted with ether (400 ml) to give a tacky precipitate. The ether was decanted and the precipitate was triturated with fresh ether (solidified). The solid was isolated by vacuum filtration, washed well with ether and converted to the free base. Thin layer chromatographic analysis (silica gel, ethyl acetate) indicated the presence of a small amount of starting amine, the product and two higher Rf spots. The mixture was separated by HPLC (silica gel; sample applied in 200 ml of dichloromethane; eluted with ethyl acetate; 200 ml/min flow rate; recycle technique utilized to optimize the separation). The appropriate fractions were combined and concentrated to give a solid (7.97 g) which was triturated with ether, filtered, and dried in vacuo at 40° C., m.p. 176°-178° C.

Workup

  1. additionA thick suspension of crystalline material
  2. customformed
  3. customa mild exothermic reaction
  4. customto give a tacky solid which
  5. customformed a gummy mass
  6. stirringOn continued stirring the material
  7. customto give a suspension
  8. customThe material was isolated by vacuum filtration
  9. washwashed well with ether
  10. extractionextracted with dichloromethane (2×250 ml)
  11. washThe combined turbid organic phase was washed once with saturated brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated to an oil
  15. concentrationA solution of the oil and toluene (150 ml) was concentrated
  16. customto remove any residual moisture
  17. additionA solution of the solid in dichloromethane (200 ml) was added
  18. stirringto stirred
  19. waitAfter three hours
  20. concentrationthe solution was concentrated
  21. customwhereupon a suspension formed
  22. customto afford a solution which
  23. waitto stand for 48 hours at room temperature
  24. concentrationThe solution was concentrated
  25. customto remove most of the dichloromethane
  26. additionthe residual oil was treated with excess ethereal hydrogen chloride
  27. additiondiluted with ether (400 ml)
  28. customto give a tacky precipitate
  29. customThe ether was decanted
  30. customthe precipitate was triturated with fresh ether (solidified)
  31. customThe solid was isolated by vacuum filtration
  32. washwashed well with ether
  33. customThe mixture was separated by HPLC (silica gel
  34. washeluted with ethyl acetate
  35. customthe separation)
  36. concentrationconcentrated

Sources & evidence

ORD record
ord-716d480f31424418a652ac9f1b97c45d
Source dataset
uspto-grants-1988_05
Patent number
US04742061

Reaction notes

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