Phosgene → tert-Butyl 2-methyl-2-[3-(4-methylsulfanyl-3-trifluoromethylphenyl)ureido]propionate

HRID 2356672Notes

Reaction equation

HRID 2356672 reaction equation
[CH3:1][C:2]1([CH3:21])[NH:6][C:5](=[O:7])[N:4]([C:8]2[CH:13]=[CH:12][C:11]([S:14][CH3:15])=[C:10]([C:16]([F:19])([F:18])[F:17])[CH:9]=2)[C:3]1=[O:20].CS[C:24]1C=CC(N)=[CH:26][C:25]=1[C:31](F)(F)F.C(Cl)(Cl)=[O:36]>C(#N)C.C1(C)C=CC=CC=1>[CH3:1][C:2]([NH:6][C:5]([NH:4][C:8]1[CH:13]=[CH:12][C:11]([S:14][CH3:15])=[C:10]([C:16]([F:19])([F:18])[F:17])[CH:9]=1)=[O:7])([CH3:21])[C:3]([O:36][C:25]([CH3:31])([CH3:26])[CH3:24])=[O:20]

Participants

6

Reactant 3

HCID 6371PhosgeneHCID 219046854-(Methylsulfanyl)-3-(trifluoromethyl)anilineHCID 578292535,5-Dimethyl-3-(4-methylsulfanyl-3-trifluoromethylphenyl)-imidazolidine-2,4-dione

Product 1

HCID 86633598tert-Butyl 2-methyl-2-[3-(4-methylsulfanyl-3-trifluoromethylphenyl)ureido]propionate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Compound 114.1 can be prepared by process “A”. To this end, 1.04 g of 4-methylsulfanyl-3-trifluoromethylphenylamine were dissolved in 25 ml of dry acetonitrile. This solution was added dropwise with stirring to a 20% solution, heated to 70° C., of phosgene in toluene, and then stirred at 80° C. for 2 h. The cooled reaction solution was concentrated under reduced pressure, and the residue was taken up with toluene and concentrated again under reduced pressure. Finally, the residue was dissolved in 25 ml of dry tetrahydrofuran and the solution was admixed with stirring with 0.88 g of tert-butyl 2-amino-2-methylpropionate hydrochloride. 1.05 ml of triethylamine were slowly added dropwise to the reaction mixture which was then stirred at room temperature for 4 h. The reaction mixture was admixed with water and extracted with ethyl acetate. The organic phase was dried over magnesium sulfate, filtered and concentrated. tert-Butyl 2-methyl-2-[3-(4-methylsulfanyl-3-trifluoromethylphenyl)ureido]propionate (molecular weight 392.13 (C17H23F3N2O3S); retention time Rt=2.40 min. [B]; MS (ESI): 337.26 (MH+−C4H8)) was obtained. The urea was dissolved in 20 ml of tetrahydrofuran, admixed with 4.9 ml of concentrated hydrochloric acid and stirred at 80° C. for 2 h. The cooled reaction mixture was concentrated under reduced pressure and the residue was admixed with ethyl acetate and water. The organic phase was removed, washed with saturated sodium hydrogen-carbonate solution and then with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel with 96/4 dichloromethane/methanol. 21.2 g (90% yield) of 5,5-dimethyl-3-(4-methylsulfanyl-3-trifluoromethylphenyl)imidazolidin-2,4-dione 114.1 were obtained. Molecular weight 318.06 (C13H13F3N2O2S); retention time Rt=1.93 min. [B]; MS (ES−): 317.07 (M−H+).

Workup

  1. additionThis solution was added dropwise
  2. customThe cooled reaction solution
  3. concentrationwas concentrated under reduced pressure
  4. concentrationconcentrated again under reduced pressure
  5. dissolutionFinally, the residue was dissolved in 25 ml of dry tetrahydrofuran
  6. stirringwith stirring with 0.88 g of tert-butyl 2-amino-2-methylpropionate hydrochloride
  7. addition1.05 ml of triethylamine were slowly added dropwise to the reaction mixture which
  8. stirringwas then stirred at room temperature for 4 h
  9. extractionextracted with ethyl acetate
  10. dry with materialThe organic phase was dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-9d3ccf0822f5435989204f3ff744d73e
Source dataset
uspto-grants-2010_07
Patent number
US07759366B2

Reaction notes

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