Triphosgene → 1-(2-Chloro-4-(trifluoromethyl)benzyl)-3-(2,3-dihydro-2-oxobenzo[d]oxazol-4-yl)urea

HRID 1505179Notes

Reaction equation

HRID 1505179 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[CH2:4][NH2:5].ClC(Cl)(O[C:18](=[O:24])[O:19][C:20](Cl)(Cl)Cl)Cl.[N-:26]=[C:27]=[O:28]>CCOC(C)=O.CN(C=O)C>[Cl:1][C:2]1[CH:9]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:7]=[CH:6][C:3]=1[CH2:4][NH:5][C:27]([NH:26][C:3]1[C:4]2[NH:5][C:18](=[O:24])[O:19][C:20]=2[CH:8]=[CH:9][CH:2]=1)=[O:28]

Participants

6

Reactant 3

HCID 94429TriphosgeneHCID 105034IsocyanateHCID 22337564(2-Chloro-4-(trifluoromethyl)phenyl)methanamine

Product 1

HCID 534761351-(2-Chloro-4-(trifluoromethyl)benzyl)-3-(2,3-dihydro-2-oxobenzo[d]oxazol-4-yl)ureaYield 10%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

Commercially available 2-chloro-4-trifluoromethylbenzylamine (572 mg, 2.7 mmol) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (809 mg, 2.7 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (5 ml) of compound 1b (270 mg, 1.8 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 70 mg of a white solid. Yield=10% 1HNMR (DMSO, 400 MHz) δ 4.45 (2H, d, J=6 Hz), 6.97 (2H, d, J=4.4 Hz), 7.07 (2H, m), 7.63 (1H, d, J=8 Hz), 7.74 (2H, d), 7.86 (1H, s), 8.61 (1H, bs), 10.90 (1H, bs); [M+1] 386.6 (C16H11ClF3N3O3 requires 385.7).

Workup

  1. additionwas added to the solution
  2. customthen evaporated
  3. dissolutiondissolved in 5 ml of DMF
  4. temperaturethe mixture was warmed at 80° C. for 8 hours
  5. customThe solvent was evaporated
  6. dissolutionthe crude was dissolved in AcOEt (30 ml)
  7. washwashed with water (1×20 ml) and brine
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe purification of the crude residue by chromatographic column

Sources & evidence

ORD record
ord-92127f4280de4b9e8d94527f1121aa83
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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