Tetrahydrofuran → 5-p-tolyl-6-(2,2,2-trifluoroethoxy)-N-((3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl)methyl)nicotinamide

HRID 1026071Notes

Reaction equation

HRID 1026071 reaction equation
Br[C:2]1[C:3]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[N:4][CH:5]=[C:6]([CH:20]=1)[C:7]([NH:9][CH2:10][C:11]1[O:15][N:14]=[C:13]([C:16]([F:19])([F:18])[F:17])[N:12]=1)=[O:8].B(O)(O)[C:28]1[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=1.C([O-])([O-])=O.[Na+].[Na+].O1CCCC1>O>[C:31]1([CH3:34])[CH:32]=[CH:33][C:28]([C:2]2[C:3]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[N:4][CH:5]=[C:6]([CH:20]=2)[C:7]([NH:9][CH2:10][C:11]2[O:15][N:14]=[C:13]([C:16]([F:19])([F:18])[F:17])[N:12]=2)=[O:8])=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 79799Tolylboronic acidHCID 866631435-bromo-6-(2,2,2-trifluoroethoxy)-N-((3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl)methyl)nicotinamide

Product 1

HCID 569292785-p-tolyl-6-(2,2,2-trifluoroethoxy)-N-((3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl)methyl)nicotinamideYield 46.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
90 °C

Procedure

5-Bromo-6-(2,2,2-trifluoroethoxy)-N-((3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl)methyl)nicotinamide (example BP; 100 mg, 223 μmol), p-tolylboronic acid (CAN 5720-05-8; 33 mg, 243 μmol), 1,1′-bis(diphenylphosphino)-ferrocene-palladium(II)dichloride dichloromethane complex (4 mg, 5.27 μmol) and Na2CO3 (35 mg, 330 μmol) were combined with tetrahydrofuran (5 mL) and water (1.5 mL). The reaction mixture was heated to 90° C., stirred for 15 h, cooled down and poured into 25 mL H2O. The mixture was extracted with ethyl acetate (2×25 mL). The organic layers were combined, washed with brine (1×25 mL), dried with MgSO4 and concentrated in vacuo. The crude material was purified twice by flash chromatography (silica gel, 20 g, 0% to 40% ethyl acetate in hexanes) to give 48 mg (46%) of the title compound as a light yellow solid; MS (ESI): 459.090 (M−H)−.

Workup

  1. temperaturecooled down
  2. extractionThe mixture was extracted with ethyl acetate (2×25 mL)
  3. washwashed with brine (1×25 mL)
  4. dry with materialdried with MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified twice by flash chromatography (silica gel, 20 g, 0% to 40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5255348c9d6c46678d4b347d96afb843
Source dataset
uspto-grants-2014_05
Patent number
US08729105B2

Reaction notes

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