Reaction #45370

Reaction equation

Oxalyl chloride

title compound

2′-{[[3,5-Bis(trifluoromethyl)benzyl](methoxycarbonyl)amino]methyl}-6-methoxy-4′-(trifluoromethyl)biphenyl-3-carboxylic acid

acetamide oxime

→

title compound

Methyl [3,5-bis(trifluoromethyl)benzyl]{[2′-methoxy-5′-(3-methyl-1,2,4-oxadiazol-5-yl)-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

Solvents

methylene chloride

Conditions

Workup

1. 1
   Concentrationthen concentrated in vacuo
2. 2
   workup.DISSOLUTIONThe crude product was re-dissolved in anhydrous dichloroethane
3. 3
   Temperatureto increase solubility
4. 4
   TemperatureThe reaction was heated to and
5. 5
   Temperaturemaintained
6. 6
   Temperatureat reflux overnight
7. 7
   TemperatureOnce the reaction cooled to room temperature
8. 8
   Otherthe solvent was removed through evaporation
9. 9
   Washwashed with water
10. 10
    Dryingbrine, dried over anhydrous sodium sulfate
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated

Procedure

Oxalyl chloride (0.14 mL, 0.28 mmol) and a few drops of dimethylformamide were added to a solution of the title compound from Example 145 (86 mg, 0.14 mmol) in methylene chloride. The reaction mixture was stirred at room temperature for 1 h then concentrated in vacuo. The crude product was re-dissolved in anhydrous dichloroethane, and acetamide oxime (16 mg, 0.21 mmol) was added along with a few drops of dimethylformamide to increase solubility. The reaction was heated to and maintained at reflux overnight. Once the reaction cooled to room temperature, the solvent was removed through evaporation. The oil was taken up in methylene chloride, washed with water, then brine, dried over anhydrous sodium sulfate, filtered and concentrated. The title compound was obtained by preparative thin layer chromatography using 50% EtOAc/hexane. 1H NMR (CDCl3, 600 MHz) δ 8.15 (s, 1H), 7.86 (s, 1H), 7.71 (s, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.43-7.56 (m, 3H), 7.35 (d, J=7.8 Hz, 1H), 7.07 (m, 1H), 4.20-4.60 (m, 4H), 3.81 (s, 3H), 3.70 (m, 3H), 2.46 (s, 3H). LC-MS (M+1) 647.9 (4.40 min).

Source