Water → {3,5-dichloro-4-[6-(3,4-dimethylphenylcarbamoyl)-1H-benzoimidazol-2-yl]-phenoxy}-acetic acid methyl ester

HRID 1514995Notes

Reaction equation

HRID 1514995 reaction equation
[CH3:1][O:2][C:3](=[O:16])[CH2:4][O:5][C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([CH:13]=O)=[C:8]([Cl:15])[CH:7]=1.[NH2:17][C:18]1[CH:19]=[C:20]([CH:32]=[CH:33][C:34]=1[NH2:35])[C:21]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH3:31])[CH:25]=1)=[O:22].C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.[Yb+3].O>CS(C)=O.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:16])[CH2:4][O:5][C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([C:13]2[NH:17][C:18]3[CH:19]=[C:20]([C:21](=[O:22])[NH:23][C:24]4[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH3:31])[CH:25]=4)[CH:32]=[CH:33][C:34]=3[N:35]=2)=[C:8]([Cl:15])[CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 2733225Ytterbium triflateHCID 66965643HCID 66965643, compoundHCID 85876215HCID 85876215, compound

Product 1

HCID 66965080{3,5-dichloro-4-[6-(3,4-dimethylphenylcarbamoyl)-1H-benzoimidazol-2-yl]-phenoxy}-acetic acid methyl ester

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3,5-dichloro-4-formylphenoxy)-acetic acid methyl ester (524 mg, 2.0 mmol) and 3,4-diamino-N-(3,4-dimethyl-phenyl)-benzamide (510 mg, 2.0 mmol) (Example 5-1, step 6) in DMSO (15 mL) was added Yb(OTf)3 (248 mg, 0.4 mmol) and the solution was stirred at ambient temperature overnight. The mixture was partioned between water and EtOAc and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with water, brine, dried with MgSO4, filtered and concentrated. Purification by HPLC (0-80% MeCN/water) gave {3,5-dichloro-4-[6-(3,4-dimethylphenylcarbamoyl)-1H-benzoimidazol-2-yl]-phenoxy}-acetic acid methyl ester as a white solid. MS (m/z) 498.1 (M+1); 1H-NMR (Methanol-d4, 400 MHz): δ 8.36 (d, 1H), 8.09 (dd, 1H), 7.87 (dd, 1H), 7.49 (d, 1H), 7.46 (dd, 1H), 7.31 (s, 2H), 7.16 (d, 1H), 4.93 (s, 2H), 3.83 (s, 3H), 2.31 (s, 3H), 2.28 (s, 3H).

Workup

  1. extractionthe aqueous layer was extracted with EtOAc
  2. washThe combined organic layers were washed with water, brine
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by HPLC (0-80% MeCN/water)

Sources & evidence

ORD record
ord-3970c3ebd2d14c3d89b7ba588f7a77de
Source dataset
uspto-grants-2012_07
Patent number
US08222248B2

Reaction notes

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