Potassium Carbonate → [5-(1-Biphenyl-4-ylmethyl-6-chloro-5-iodo-1H-benzoimidazol-2-yloxy)-2-methyl-phenyl]-phosphonic acid diethyl ester

HRID 1960151Notes

Reaction equation

HRID 1960151 reaction equation
[C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[C:12]3[CH:13]=[C:14]([Cl:18])[C:15]([I:17])=[CH:16][C:11]=3[N:10]=[C:9]2S(C)(=O)=O)=[CH:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+].[CH2:35]([O:37][P:38]([C:43]1[CH:48]=[C:47]([OH:49])[CH:46]=[CH:45][C:44]=1[CH3:50])(=[O:42])[O:39][CH2:40][CH3:41])[CH3:36]>CN(C=O)C>[CH2:40]([O:39][P:38]([C:43]1[CH:48]=[C:47]([O:49][C:9]2[N:8]([CH2:7][C:4]3[CH:5]=[CH:6][C:1]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:2][CH:3]=3)[C:12]3[CH:13]=[C:14]([Cl:18])[C:15]([I:17])=[CH:16][C:11]=3[N:10]=2)[CH:46]=[CH:45][C:44]=1[CH3:50])(=[O:42])[O:37][CH2:35][CH3:36])[CH3:41]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 57481474Diethyl 5-hydroxy-2-methylphenylphosphonateHCID 673776421-Biphenyl-4-ylmethyl-6-chloro-5-iodo-2-methanesulfonyl-1H-benzoimidazole

Product 1

HCID 86761791[5-(1-Biphenyl-4-ylmethyl-6-chloro-5-iodo-1H-benzoimidazol-2-yloxy)-2-methyl-phenyl]-phosphonic acid diethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-biphenyl-4-ylmethyl-6-chloro-5-iodo-2-methanesulfonyl-1H-benzoimidazole (1.2 g, 2.3 mmol) in DMF (10 ml) at rt was added K2CO3 (635 mg, 4.6 mmol), followed by (5-hydroxy-2-methyl-phenyl)-phosphonic acid diethyl ester (630 mg, 2.6 mmol). The mixture was stirred overnight at rt. The solvent was then removed on a rotary evaporator. The resulting residue was partitioned between EtOAc and a solution of half-saturated ammonium chloride. The EtOAc layer was washed with H2O, brine, and then dried with MgSO4. After rotary evaporation, the residue was purified by flash chromatography (SiO2, 12 g). The title compound was eluted with a gradient up to 50% EtOAc in Hexane as a mixture of the two protected regioisomers.

Workup

  1. customThe solvent was then removed on a rotary evaporator
  2. customThe resulting residue was partitioned between EtOAc
  3. washThe EtOAc layer was washed with H2O, brine
  4. dry with materialdried with MgSO4
  5. customAfter rotary evaporation
  6. customthe residue was purified by flash chromatography (SiO2, 12 g)
  7. washThe title compound was eluted with a gradient up to 50% EtOAc in Hexane as a mixture of the two protected regioisomers

Sources & evidence

ORD record
ord-63a648e8322049c5935b34662b69866e
Source dataset
uspto-grants-2013_04
Patent number
US08410284B2

Reaction notes

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