Potassium Carbonate → 5-Cyclopropyl-4-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxymethyl]-3-(2-trifluoromethoxy-phenyl)-isoxazole

HRID 250279Notes

Reaction equation

HRID 250279 reaction equation
Br[CH2:2][C:3]1[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[O:17][C:18]([F:21])([F:20])[F:19])=[N:5][O:6][C:7]=1[CH:8]1[CH2:10][CH2:9]1.[CH3:22][C:23]1[CH:24]=[C:25]([OH:38])[CH:26]=[CH:27][C:28]=1[B:29]1[O:33][C:32]([CH3:35])([CH3:34])[C:31]([CH3:37])([CH3:36])[O:30]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH:8]1([C:7]2[O:6][N:5]=[C:4]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][C:18]([F:21])([F:20])[F:19])[C:3]=2[CH2:2][O:38][C:25]2[CH:26]=[CH:27][C:28]([B:29]3[O:33][C:32]([CH3:34])([CH3:35])[C:31]([CH3:37])([CH3:36])[O:30]3)=[C:23]([CH3:22])[CH:24]=2)[CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 574432723-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 669060924-(Bromomethyl)-5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]isoxazole

Product 1

HCID 672723615-Cyclopropyl-4-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxymethyl]-3-(2-trifluoromethoxy-phenyl)-isoxazole

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
10 °C

Procedure

To a 5-L 3-neck round bottom flask with a mechanical stirrer, thermocouple, reflux condenser, and drying tube is added 4-bromomethyl-5-cyclopropyl-3-(2-trifluoromethoxy-phenyl)-isoxazole (221.7 g, 0.612 mol, 1.05 eq), acetonitrile (2 L), 3-Methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (136.5 g, 0.583 mol, 1 eq) and potassium carbonate (241.8 g, 1.749 mol, 3 eq). The reaction mixture is heated to reflux and stirred at this temperature for 1 hour. Upon completion of the reaction, as evidenced by thin layer chromatography, the reaction mixture is cooled to 0-20° C. The reaction mixture is filtered and the filter cake is washed with acetonitrile (2×100 mL). The reaction mixture is concentrated under reduced pressure to a solid which is co-evaporated with 1,4-dioxane (500 mL). The title compound is used without further purification. 1H NMR (DMSO-d6, 300 MHz): δ 7.7-7.5 (m, 5H), 6.61 (m, 2H), 4.90 (s, 2H), 2.39 (m, 1H), 2.36 (s, 3H), 1.24 (s, 12H), 1.10 (m, 4H).

Workup

  1. temperatureTo a 5-L 3-neck round bottom flask with a mechanical stirrer, thermocouple, reflux condenser
  2. customdrying tube
  3. temperatureThe reaction mixture is heated
  4. temperatureto reflux
  5. customUpon completion of the reaction
  6. filtrationThe reaction mixture is filtered
  7. washthe filter cake is washed with acetonitrile (2×100 mL)
  8. concentrationThe reaction mixture is concentrated under reduced pressure to a solid which
  9. customThe title compound is used without further purification

Sources & evidence

ORD record
ord-ad958508a68b4fedb8d806a829f363ed
Source dataset
uspto-grants-2011_01
Patent number
US07863302B2

Reaction notes

Loading…