1,2-Dimethoxyethane → HCID 15947284, compound

HRID 1466438Notes

Reaction equation

HRID 1466438 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([C:13]([OH:16])([CH3:15])[CH3:14])[N:10]=[C:9]2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH:23]([CH3:25])[CH3:24])=[CH:4][CH:3]=1.[CH3:26][S:27]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)(=[O:29])=[O:28].C([O-])([O-])=O.[K+].[K+].COCCOC>CCOC(C)=O.O>[CH:23]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:9]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([C:34]3[CH:33]=[CH:32][CH:31]=[C:30]([S:27]([CH3:26])(=[O:29])=[O:28])[CH:35]=3)=[CH:3][CH:4]=2)[CH:12]=[C:11]([C:13]([OH:16])([CH3:15])[CH3:14])[N:10]=1)([CH3:25])[CH3:24]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 59251233HCID 59251233, compound

Product 1

HCID 15947284HCID 15947284, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a 50 mL round bottom flask attached with Vigreux column and magnetic stir bar was added 2-[1-(4-Bromo-phenyl)-2-(2-isopropyl-phenyl)-1H-imidazol-4-yl]-propan-2-ol (297 mg, 743 μmol), 3-methylsulfonylphenyl boronic acid (193 mg, 968 μmol), PdCl2dppf (60 mg, 10 mol %), K2CO3 (310 mg, 2.23 mmol), 1,2-dimethoxyethane (14 mL) and H2O (4 mL). The reaction solution was allowed to stir at 80° C. for 2 hrs. The reaction solution was diluted with EtOAc (150 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 (100 mL) and aq NaCl (100 mL). The organic phase was dried over Na2SO4, filtered, concentrated on the Rotavapor and chromatographed through a 25 g SiO2 column using a mobile phase gradient of 100% Hx to 90% EtOAc to afford 303 mg (86% yield) of the title compound. 1H NMR (400 MHz, DMSO-d6): δ 8.14 (s, 1H), 8.02 (d, 1H), 7.89 (d, 1H), 7.89 (d, 1H), 7.78 (d, 2H), 7.72 (t, 1H), 7.37-7.34 (m, 3H), 7.26 (d, 2H), 7.18-7.16 (m, 2H), 4.84 (s, 1H), 3.26 (s, 3H), 2.85 (sept, 1H), 1.50 (6H), 0.96 (d, 6H); MS (ES): 475.4 [M+H]+, 497.5 [M+Na]+.

Workup

  1. customTo a 50 mL round bottom flask attached with Vigreux column and magnetic stir bar
  2. filtrationfiltered through a Celite
  3. customto remove
  4. customThe filtrate was transferred to a separatory funnel
  5. washwashed with aq NH4Cl (100 mL) and aq NaCl (100 mL)
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated on the Rotavapor
  9. customchromatographed through a 25 g SiO2 column

Sources & evidence

ORD record
ord-d441b42fbcda44ccbbff44be14130245
Source dataset
uspto-grants-2015_04
Patent number
US09000022B2

Reaction notes

Loading…