4-(Trifluoromethyl)benzylamine → HCID 53476469, compound

HRID 1505194Notes

Reaction equation

HRID 1505194 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)(OC(=O)OC(Cl)(Cl)Cl)Cl.[N-:25]=[C:26]=[O:27].N[C:29]1[C:34]2[O:35][CH2:36][C:37](=[O:39])[NH:38][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:26]([NH:25][C:29]2[C:34]3[O:35][CH2:36][C:37](=[O:39])[NH:38][C:33]=3[CH:32]=[CH:31][CH:30]=2)=[O:27])=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 768044-(Trifluoromethyl)benzylamineHCID 94429TriphosgeneHCID 105034IsocyanateHCID 115934888-Amino-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 53476469HCID 53476469, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

Commercially available 4-trifluoromethylbenzylamine (0.6 ml, 4.2 mmol) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (1.2 g, 4.2 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 1f (460 mg, 2.8 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 250 mg of a white solid. Yield=24% 1HNMR (DMSO, 200 MHz) δ 4.31 (2H, d, J=6.2 Hz), 6.46 (1H, dd), 6.70 (2H, t), 6.81 (1H, t), 7.45 (2H, d, J=8 Hz), 7.70 (4H, m), 8.16 (1H, s), 10.72 (1H, bs); [M+1] 366.1 (C17H14F3N3O3 requires 365.3).

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-a55af40506224995bf1a697c9b6abb63
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

Loading…