N,N-Dimethylaniline → N-[4,5-Dimethoxy-2-(methylthio)phenyl]-1-pyrrolidinecarboxamide

HRID 426708Notes

Reaction equation

HRID 426708 reaction equation
[C:1](Cl)(Cl)=[O:2].C[N:6]([CH3:13])[C:7]1[CH:12]=[CH:11]C=CC=1.[CH3:14][S:15][C:16]1[CH:22]=[C:21]([O:23][CH3:24])[C:20]([O:25][CH3:26])=[CH:19][C:17]=1[NH2:18]>C1(C)C=CC=CC=1>[N:6]1([C:1]([NH:18][C:17]2[CH:19]=[C:20]([O:25][CH3:26])[C:21]([O:23][CH3:24])=[CH:22][C:16]=2[S:15][CH3:14])=[O:2])[CH2:7][CH2:12][CH2:11][CH2:13]1

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 6371PhosgeneHCID 608034HCID 608034, compound

Product 1

HCID 12694257N-[4,5-Dimethoxy-2-(methylthio)phenyl]-1-pyrrolidinecarboxamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

A solution of 24 g. of phosgene in toluene was added rapidly to a solution of 58.1 g. of N,N-dimethylaniline in 500 ml. of toluene, which solution has been previously cooled to about 0° C. with an ice-water bath. After stirring the resulting solution for about five minutes, a solution of 39.8 g. of 2-methylthio-4,5-dimethoxyaniline in 350 ml. of toluene was added on dropwise fashion over a 30 minute period to the cooled, stirred reaction mixture. The reaction mixture was allowed to warm to ambient temperature, at which temperature it was stirred for an additional four hours. The reaction mixture was then filtered, and the filtrate concentrated under reduced pressure to a thick oil. The oil was dissolved in 1 l. of acetonitrile and 50 ml. of pyrrolidine were added thereto. This new reaction mixture was stirred for about 20 hours, after which time it was concentrated under reduced pressure to a thick oil. The residual oil was dissolved in 1 l. of methylene chloride. The methylene chloride solution was washed twice with 5 percent aqueous hydrochloric acid and once with water. The methylene chloride solution was then dried and the solvent removed therefrom in vacuo, leaving a solid residue comprising N-pyrrolidinylcarbonyl-2-methylthio-4,5-dimethoxyaniline. Recrystallization of the solid from a benzene-hexane solvent mixture yield crystalline material melting at 141°-3° C. (91 percent yield).

Workup

  1. stirringstirred
  2. customreaction mixture
  3. stirringwas stirred for an additional four hours
  4. filtrationThe reaction mixture was then filtered
  5. concentrationthe filtrate concentrated under reduced pressure to a thick oil
  6. dissolutionThe oil was dissolved in 1 l
  7. additionof pyrrolidine were added
  8. stirringThis new reaction mixture was stirred for about 20 hours
  9. concentrationafter which time it was concentrated under reduced pressure to a thick oil
  10. dissolutionThe residual oil was dissolved in 1 l
  11. washThe methylene chloride solution was washed twice with 5 percent aqueous hydrochloric acid and once with water
  12. dry with materialThe methylene chloride solution was then dried
  13. customthe solvent removed

Sources & evidence

ORD record
ord-6eab6d85d7914c5e90804297f78f641b
Source dataset
uspto-grants-1979_10
Patent number
US04171361

Reaction notes

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