Cesium carbonate → methyl 3-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)benzoate

HRID 1475212Notes

Reaction equation

HRID 1475212 reaction equation
[CH3:1][C:2]1[NH:6][N:5]=[C:4]([C:7]2[O:11][N:10]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([O:18][C:19]([F:22])([F:21])[F:20])=[CH:14][CH:13]=3)[N:8]=2)[N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:30][C:31]1[CH:32]=[C:33]([CH:38]=[CH:39][CH:40]=1)[C:34]([O:36][CH3:37])=[O:35]>CS(C)=O.O>[CH3:1][C:2]1[N:6]([CH2:30][C:31]2[CH:32]=[C:33]([CH:38]=[CH:39][CH:40]=2)[C:34]([O:36][CH3:37])=[O:35])[N:5]=[C:4]([C:7]2[O:11][N:10]=[C:9]([C:12]3[CH:13]=[CH:14][C:15]([O:18][C:19]([F:22])([F:20])[F:21])=[CH:16][CH:17]=3)[N:8]=2)[N:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 517981Methyl 3-(bromomethyl)benzoateHCID 867118775-(5-methyl-1H-1,2,4-triazol-3-yl)-3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazole

Product 1

HCID 86711907methyl 3-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)benzoateYield 68%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of 5-(5-methyl-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole (311 mg, 1.0 mmol) in DMSO (5 mL), Cs2CO3 (652 mg, 2.0 mmol) and methyl 3-(bromomethyl)benzoate (252 mg, 1.1 mmol) were added at RT. The mixture was stirred at RT for 2 h. The resulting mixture was diluted with H2O (20 mL) and extracted with EtOAc (4×40 mL). The combined organic layers werewashed with H2O (20 mL) and brine (2×20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure, and the residue was purified by a silica gelchromatography (EtOAc/Hexane 10% to 60% EtOAc) to give methyl 3-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)benzoate as a white solid (310 mg, 68%). MS (ES+) C21H16F3N5O4 requires: 459. found: 460 [M+H]+; 1H NMR (600 MHz, CDCl3) δ 8.29 (d, J=8.8 Hz, 2H), 8.04 (d, J=7.4 Hz, 1H), 7.95 (s, 1H), 7.48 (t, J=7.5 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.34 (d, J=8.3 Hz, 2H), 5.51 (s, 2H), 3.92 (s, 3H), 2.55 (s, 3H).

Workup

  1. extractionextracted with EtOAc (4×40 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customthe residue was purified by a silica gelchromatography (EtOAc/Hexane 10% to 60% EtOAc)

Sources & evidence

ORD record
ord-cbe97a6db503484e9871f81f59f87682
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

Loading…