Toluene → HCID 15947595, compound

HRID 1466435Notes

Reaction equation

HRID 1466435 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[N:10]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([S:30]([CH3:33])(=[O:32])=[O:31])[CH:25]=3)=[CH:20][CH:19]=2)[CH:11]=[C:12]([C:14](O)([CH3:16])[CH3:15])[N:13]=1.C1(C)C=CC=CC=1>C(O)(=O)C>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[C:9]1[N:10]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([S:30]([CH3:33])(=[O:32])=[O:31])[CH:25]=3)=[CH:20][CH:19]=2)[CH:11]=[C:12]([C:14]([CH3:16])=[CH2:15])[N:13]=1

Participants

4

Reactant 2

HCID 1140TolueneHCID 59251431HCID 59251431, compound

Product 1

HCID 15947595HCID 15947595, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a 25 mL round bottom flask attached with Vigreux column was added 2-[2-(2,6-Dichloro-phenyl)-1-(3′-methanesulfonyl-biphenyl-4-yl)-1H-imidazol-4-yl]-propan-2-ol (383 mg, 764 μmol), anhydrous toluene (8 mL) and acetic acid (3.5 mL). The reaction solution was allowed to stir at reflux for 1.5 hr. The cooled reaction solution was concentrated in vacuo, and the residue was taken into EtOAc (200 mL) and washed with aq NaHCO3 (100 mL×2) and aq. NaCl (100 mL). The organic phase was partitioned, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was chromatographed through a 25 g SiO2 column using a mobile gradient of 100% Hx to 80% EtOAc to provide 288 mg (78% yield) of title compound. 1H NMR. (400 MHz, DMSO-d6): δ 8.15 (br s, 1H), 8.08-7.97 (m, 2H), 7.92 (d, 1H), 7.89 (d, 2H), 7.75 (t, 1H), 7.64-7.57 (m, 3H), 7.43 (d, 2H), 5.77 (br s, 1H), 5.10 (br s, 1H), 3.29 (s, 3H), 2.11 (s, 3H); MS (ES): 483.1, 485.1 [M+H]+.

Workup

  1. customTo a 25 mL round bottom flask attached with Vigreux column
  2. temperatureat reflux for 1.5 hr
  3. customThe cooled reaction solution
  4. concentrationwas concentrated in vacuo
  5. washwashed with aq NaHCO3 (100 mL×2) and aq. NaCl (100 mL)
  6. customThe organic phase was partitioned
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was chromatographed through a 25 g SiO2 column

Sources & evidence

ORD record
ord-668a260637b14110a3b00b84df275351
Source dataset
uspto-grants-2015_04
Patent number
US09000022B2

Reaction notes

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