Triphosgene → HCID 53476136, compound

HRID 1505180Notes

Reaction equation

HRID 1505180 reaction equation
[F: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>[F: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 2734878(4-Fluoro-2-(trifluoromethyl)phenyl)methanamine

Product 1

HCID 53476136HCID 53476136, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

Commercially available 4-fluoro-2-trifluoromethylbenzylamine (0.5 ml, 3.7 mmol) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (1.12 g, 3.7 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 (360 mg, 2.4 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 90 mg of a white solid. Yield=10% 1HNMR (DMSO, 200 MHz) δ 4.36 (2H, d, J=5.6 Hz), 6.71 (1H, t, J=6 Hz), 6.98 (2H, m), 7.56 (4H, m), 8.55 (1H, bs), 11.09 (1H, bs); [M+1] 370.2 (C16H11F4N3O3 requires 369.27).

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-6459908eb24f4cc4ae0c6fe32659814b
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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