4-(Trifluoromethyl)benzylamine → HCID 67424958, compound

HRID 1505211Notes

Reaction equation

HRID 1505211 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH2:8])=[CH:5][CH:4]=1.ClC(Cl)(O[C:17](=[O:23])[O:18][C:19](Cl)(Cl)Cl)Cl.[N-]=C=O.OC1[C:38]2[NH:37][C:36](=[O:39])[CH2:35][O:34][C:33]=2[CH:32]=[CH:31][CH:30]=1>CCOC(C)=O.CN(C=O)C>[F:1][C:2]([F:11])([F:12])[C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH:8][C:17](=[O:23])[O:18][C:19]2[C:38]3[NH:37][C:36](=[O:39])[CH2:35][O:34][C:33]=3[CH:32]=[CH:31][CH:30]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 768044-(Trifluoromethyl)benzylamineHCID 94429TriphosgeneHCID 105034IsocyanateHCID 457898075-Hydroxy-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 67424958HCID 67424958, compoundYield 45.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
80 °C

Procedure

4-trifluoromethylbenzylamine (0.52 ml, 3.6 mmol) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (1 g, 3.6 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 (10 ml) of compound 25 (400 mg, 2.42 mmol) and TEA (0.34 ml, 1 equiv.) and the mixture was stirred at rt for 8 hours. (TLC AcOEt 1/petroleum ether 1). 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 400 mg of a white solid. Yield=45% 1HNMR (DMSO, 200 MHz) δ 4.38 (2H, d, J=6.4 Hz), 4.57 (2H, s), 6.85 (3H, m), 7.59 (2H, d, J=8.2 Hz), 7.72 (2H, d, J=8.4 Hz), 8.15 (1H, bt), 10.61 (1H, bs); [M+1] 367.1 (C17H13F3N2O4 requires 366.3).

Workup

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

Sources & evidence

ORD record
ord-eb79f08478b54461a6dac97cd45d3b99
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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