1,4-Dioxane → {4-[1-(4-pentafluoroethyloxyphenyl)-1H-[1,2,4]triazol-3-yl]-phenyl}-carbamic acid tert-butyl ester

HRID 2207011Notes

Reaction equation

HRID 2207011 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:11][CH:10]=2)O1.Br[C:25]1[N:29]=[CH:28][N:27]([C:30]2[CH:35]=[CH:34][C:33]([O:36][C:37]([F:43])([F:42])[C:38]([F:41])([F:40])[F:39])=[CH:32][CH:31]=2)[N:26]=1.C([O-])(O)=O.[Na+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:43][C:37]([F:42])([O:36][C:33]1[CH:34]=[CH:35][C:30]([N:27]2[CH:28]=[N:29][C:25]([C:9]3[CH:10]=[CH:11][C:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[CH:13][CH:14]=3)=[N:26]2)=[CH:31][CH:32]=1)[C:38]([F:41])([F:40])[F:39]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 2734617tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamateHCID 893818873-bromo-1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazole

Product 1

HCID 86668344{4-[1-(4-pentafluoroethyloxyphenyl)-1H-[1,2,4]triazol-3-yl]-phenyl}-carbamic acid tert-butyl esterYield 68.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
140 °C

Procedure

A microwave vial was charged with tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (178 mg, 0.559 mmol), 3-bromo-1-(4-(pentafluoroethoxy)phenyl)-1H-1,2,4-triazole (200 mg, 0.559 mmol), NaHCO3 (94 mg, 1.2 mmol), and Pd(PPh3)4 (39 mg, 0.034 mmol). Dioxane (3.8 mL) and water (1.2 mL) were added, and the capped reaction mixture was heated at 140° C. for 30 min in a Biotage Initiator® microwave reactor with external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was cooled to RT, and allowed to stand overnight. Water (3 mL) was added to the solution, and a gummy solid formed, which was filtered and air-dried. Recrystallization of this material from MeOH/water gave the title compound as a white solid (180 mg, 66%): 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.12 (d, J=8.7 Hz, 2H), 7.80 (d, J=9.0 Hz, 2H), 7.48 (d, J=8.7 Hz, 2H), 7.39 (d, J=8.9 Hz, 2H), 6.61 (s, 1H), 1.54 (s, 9H); 19F NMR (376 MHz, CDCl3) 5-85.90, −87.86; ESIMS m/z 470 ([M+H]+)

Workup

  1. customthe capped reaction mixture
  2. temperatureThe reaction mixture was cooled to RT
  3. customa gummy solid formed
  4. filtrationwhich was filtered
  5. customair-dried
  6. customRecrystallization of this material from MeOH/water

Sources & evidence

ORD record
ord-f02363b3fa034990b191151a9205983e
Source dataset
uspto-grants-2016_06
Patent number
US09376401B2

Reaction notes

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