1,4-Dioxane → HCID 71212633, compound

HRID 924280Notes

Reaction equation

HRID 924280 reaction equation
Br[C:2]1[N:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([O:13][C:14]([F:17])([F:16])[F:15])=[CH:9][CH:8]=2)[N:3]=1.[CH3:18][C:19]1[CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=[CH:23][C:20]=1[CH:21]=[O:22].C(=O)(O)[O-].[Na+].O1CCOCC1>C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[CH3:18][C:19]1[CH:26]=[C:25]([C:2]2[N:6]=[CH:5][N:4]([C:7]3[CH:12]=[CH:11][C:10]([O:13][C:14]([F:17])([F:16])[F:15])=[CH:9][CH:8]=3)[N:3]=2)[CH:24]=[CH:23][C:20]=1[CH:21]=[O:22]

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 712094283-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazoleHCID 900205021527505-56-1

Product 1

HCID 71212633HCID 71212633, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

3-Bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (C1) (0.30 g, 1.0 mmol), 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (CB4) (0.25 g, 1.0 mmol), sodium bicarbonate (0.25 g, 2.9 mmol), tetrakis(triphenylphosphine) palladium(0) (0.17 g, 0.15 mmol), dioxane (3.9 mL), and water (0.97 mL). in a 0.5-2.0 mL vial was capped and heated at 140° C. for 30 minutes in a Biotage Initiator® microwave reactor with external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography using 0-20% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent provided the title compound as a white solid (0.19 g, 57%): 1H NMR (400 MHz, CDCl3) δ 10.33 (s, 1H), 8.61 (s, 1H), 8.19 (dd, J=8.0, 1.6 Hz, 1H), 8.13 (t, J=1.1 Hz, 1H), 7.92 (d, J=8.0 Hz, 1H), 7.86-7.78 (m, 2H), 7.45-7.37 (m, 2H), 2.77 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −58.01; ESIMS m/z 348 ([M+H]+)

Workup

  1. customin a 0.5-2.0 mL vial was capped
  2. washwashed with water
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. additionThe organic layers were poured through a phase separator
  5. concentrationconcentrated
  6. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-30e5085199ef47aeb6ae0efc51bd4cf7
Source dataset
uspto-grants-2016_03
Patent number
US09278964B2

Reaction notes

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