3,4-Dichlorobenzyl chloride → 1-dimethylamino-N-[3,4-dichlorotolyl]-cyclohexane carboxamide

HRID 2072019Notes

Reaction equation

HRID 2072019 reaction equation
[H-].[Na+].[CH3:3][N:4]([CH3:14])[C:5]1([C:11]([NH2:13])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.[Cl:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1[Cl:24])[CH2:19]Cl>CN(C)C=O.Cl.CCOCC>[CH3:3][N:4]([CH3:14])[C:5]1([C:11]([NH:13][C:17]2[C:16]([Cl:15])=[C:23]([Cl:24])[CH:22]=[CH:21][C:18]=2[CH3:19])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

7

Reactant 3

HCID 76093,4-Dichlorobenzyl chlorideHCID 24758Sodium hydrideHCID 20489818HCID 20489818, compound

Product 1

HCID 867338441-dimethylamino-N-[3,4-dichlorotolyl]-cyclohexane carboxamide

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (0.8 g., 50% dispersion in oil) was added to a solution of 1-dimethylaminocyclohexane carboxamide (2 g.) in dimethylformamide (40 ml.) and the mixture stirred for 2 hrs. A solution of 3,4-dichlorobenzyl chloride (2.4 g.) in dimethylformamide (10 ml.) was added dropwise and the resulting mixture stirred overnight. The mixture was filtered and the filtrate evaporated to dryness. Petrol (80/100) was added, the mixture boiled, and the solid filtered off. The filtrate was decolourised with activated charcoal and evaporated to dryness to leave a colourless oil. The oil was dissolved in 2N hydrochloric acid and washed with benzene (4 × 200 ml.). The aqueous phase was basified (2N NaOH) and extracted with benzene (4 × 200 ml.). The benzene extracts were washed with water, (4 × 200 ml.) dried (Na2SO4) and evaporated to leave a colourless oil (2.1 g.), shown by T.L.C. (silica/ether) to consist of three components. The oil was dissolved in the minimum of ether and chromatographed on a column of silica (50 × 2.0 cms.) eluting with ether (11 × 100 ml. fractions). Fractions 3-11 were combined, evaporated to dryness and rechromatographed as above. Combination and evaporation of the appropriate fractions afforded a white crystalline solid (1.315 g., 35%). Recrystallisation from 40/60 petrol afforded 1-dimethylamino-N-[3,4-dichlorotolyl]-cyclohexane carboxamide as white needles (0.846 g.) m.p. 82°-83° C. A second crop (0.091 g.) melted at 78°-83° C.

Workup

  1. stirringthe resulting mixture stirred overnight
  2. filtrationThe mixture was filtered
  3. customthe filtrate evaporated to dryness
  4. additionPetrol (80/100) was added
  5. filtrationthe solid filtered off
  6. customevaporated to dryness
  7. customto leave a colourless oil
  8. washwashed with benzene (4 × 200 ml.)
  9. extractionextracted with benzene (4 × 200 ml.)
  10. washThe benzene extracts were washed with water, (4 × 200 ml.)
  11. dry with materialdried (Na2SO4)
  12. customevaporated
  13. customto leave a colourless oil (2.1 g.)
  14. customchromatographed on a column of silica (50 × 2.0 cms.)
  15. washeluting with ether (11 × 100 ml. fractions)
  16. customevaporated to dryness
  17. customrechromatographed as above
  18. customCombination and evaporation of the appropriate fractions
  19. customafforded a white crystalline solid (1.315 g., 35%)
  20. customRecrystallisation from 40/60 petrol

Sources & evidence

ORD record
ord-711540c0a2a143caa25da0988a61ba91
Source dataset
uspto-grants-1977_09
Patent number
US04049663

Reaction notes

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