1,2-Dimethoxyethane → HCID 15947284, compound

HRID 1046653Notes

Reaction equation

HRID 1046653 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.Cl[Pd]Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].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

8

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 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 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), PdCl2 dppf (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-746f646451f04b0a9f70d82c9e816225
Source dataset
uspto-grants-2013_10
Patent number
US08569352B2

Reaction notes

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