Triphosgene → HCID 53476137, compound

HRID 1505181Notes

Reaction equation

HRID 1505181 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=1.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]=[CH:8][C:5]([CH2:6][NH:7][C:27]([NH:26][C:5]2[C:6]3[NH:7][C:18](=[O:24])[O:19][C:20]=3[CH:2]=[CH:3][CH:4]=2)=[O:28])=[C:4]([C:10]([F:11])([F:12])[F:13])[CH:3]=1

Participants

6

Reactant 3

HCID 94429TriphosgeneHCID 105034IsocyanateHCID 177508301-[4-Chloro-2-(trifluoromethyl)phenyl]methanamine

Product 1

HCID 53476137HCID 53476137, compoundYield 9.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

Commercially available 4-chloro-2-trifluoromethylbenzylamine (1 g, 4.77 mmol) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (1.41 g, 4.77 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (5 ml) of compound 1b (475 mg, 3.2 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt 4/petroleum ether 6). 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 120 mg of a white solid. Yield=9.7% 1HNMR (DMSO, 200 MHz) δ 4.45 (2H, d, J=5.6 Hz), 6.99 (4H, m), 7.65 (1H, d), 7.73 (1H, d), 7.85 (1H, bs), 8.62 (1H, bs), 11.04 (1H, bs); [M+1] 386.6 (C16H11ClF3N3O3 requires 385.73).

Workup

  1. additionwas added to the solution
  2. customthen evaporated
  3. dissolutionthe residue was dissolved 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-8e4ba23b108e4dc1b3bdf7f56ab7884d
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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