1,4-Dioxane → benzyl 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylcarbamate

HRID 573813

Reaction equation

HRID 573813 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.CC1(C)C(C)(C)OB([C:26]2[CH:43]=[CH:42][C:29]([CH2:30][NH:31][C:32](=[O:41])[O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:28][CH:27]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>[Cl-].[Na+].O.O>[F:15][C:14]([F:17])([F:16])[O:13][C:10]1[CH:11]=[CH:12][C:7]([N:4]2[CH:5]=[N:6][C:2]([C:26]3[CH:43]=[CH:42][C:29]([CH2:30][NH:31][C:32](=[O:41])[O:33][CH2:34][C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)=[CH:28][CH:27]=3)=[N:3]2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 712094283-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazoleHCID 90404705benzyl N-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}carbamate

Product 1

HCID 90404490benzyl 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylcarbamateYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
65 °C

Procedure

In a 50 mL round bottomed flask, equipped with a magnetic stir bar, 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (C1) (1.0 g, 3.3 mmol), benzyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate (C13) (1.3 g, 3.6 mmol), bistriphenylphosphine dichloropalladium(II) (0.120 g, 0.171 mmol), and potassium phosphate (1.38 g, 6.49 mmol) were charged as solids. The flask was sealed and placed under nitrogen atmosphere. Dioxane (17.3 mL) and water (4.3 mL) were added. The reaction was warmed to an internal temperature of 65° C. for 18 hours. The reaction mixture was cooled to room temperature, poured into a brine solution and extracted with ethyl acetate (3×75 mL). The combined organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrated. The resulting residue was purified via flash column chromatography using 0-50% ethyl acetate/hexanes as eluent to afford the title compound as a white solid (0.850 g, 56%): 1H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 8.17-8.00 (m, 4H), 7.91 (t, J=6.2 Hz, 1H), 7.72-7.59 (m, 2H), 7.46-7.12 (m, 7H), 5.07 (s, 2H), 4.29 (d, J=6.1 Hz, 2H); 19F NMR (376 MHz, DMSO-d6) δ −56.96; ESIMS m/z 469 ([M+H]+).

Workup

  1. customIn a 50 mL round bottomed flask, equipped with a magnetic stir bar
  2. customThe flask was sealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. extractionextracted with ethyl acetate (3×75 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified via flash column chromatography

Sources & evidence

ORD record
ord-9a80c9c109104691ad3c50a83dfa8f7a
Source dataset
uspto-grants-2015_05
Patent number
US09029560B2

Linked notes

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