1,2-Dimethoxyethane → HCID 44177698, compound

HRID 1673037Notes

Reaction equation

HRID 1673037 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([C:13]3[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[O:15][N:14]=3)[N:10]=[C:9]2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[Cl:28])=[C:4]([Cl:29])[CH:3]=1.[CH3:30][S:31]([C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1)(=[O:33])=[O:32].C([O-])([O-])=O.[K+].[K+].COCCOC>CCOC(C)=O.O>[Cl:29][C:4]1[CH:3]=[C:2]([C:38]2[CH:37]=[CH:36][CH:35]=[C:34]([S:31]([CH3:30])(=[O:33])=[O:32])[CH:39]=2)[CH:7]=[CH:6][C:5]=1[N:8]1[CH:12]=[C:11]([C:13]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[O:15][N:14]=2)[N:10]=[C:9]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[Cl:28]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 59240453HCID 59240453, compound

Product 1

HCID 44177698HCID 44177698, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To an 8 mL glass vial was added 3-(1-(4-bromo-2-chlorophenyl)-2-(2-chlorophenyl)-1H-imidazol-4-yl)-5-(trifluoromethyl)isoxazole (120 mg, 236 μmol), 3-methylsulfonylphenyl boronic acid (52 mg, 260 μmol), PdCl2dppf (20 mg, 10 mol %), K2CO3 (100 mg, 708 μmol), 1,2-dimethoxyethane (6 mL) and H2O (1.5 mL). The reaction solution was allowed to stir at 80° C. for 2.5 hrs. The reaction solution was diluted with EtOAc (30 mL) and filtered through a celite padded Buchner funnel to remove spent Pd. The filtrate was transferred to a separatory funnel and washed with aq NH4Cl (40 mL) and aq NaCl (40 mL). The organic phase was dried over Na2SO4, filtered, concentrated on the Rotavapor and chromatographed through a 12 g SiO2 column using a mobile phase gradient of 5% EtOAc to 100% EtOAc to afford 72 mg (53% yield) of the title compound. MS (ESI) 578.0, 580.0 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.93 (s, 1H), 8.38 (s, 1H), 8.21 (s, 1H), 8.13 (d, J=8 Hz, 1H), 8.08 (s, 1H), 7.96 (d, J=8 Hz, 1H), 7.71-7.79 (m, 2H), 7.69 (d, J=7 Hz, 1H), 7.62 (d, J=8 Hz, 1H), 7.48 (m, 1H), 7.36-7.42 (m, 2H), 3.34 (s, 3H) ppm; 19F NMR (400 MHz, DMSO-d6) 6-81.9 ppm.

Workup

  1. filtrationfiltered through a celite
  2. customto remove
  3. customThe filtrate was transferred to a separatory funnel
  4. washwashed with aq NH4Cl (40 mL) and aq NaCl (40 mL)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated on the Rotavapor
  8. customchromatographed through a 12 g SiO2 column

Sources & evidence

ORD record
ord-1062a82501844089a2848f1ef0363dd2
Source dataset
uspto-grants-2011_08
Patent number
US07998995B2

Reaction notes

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