Potassium Carbonate → [6-Chloro-5-(4-chloro-3-methyl-phenyl)-1H-benzoimidazol-2-ylsulfanylmethyl]-phosphonic acid diethyl ester

HRID 2193854Notes

Reaction equation

HRID 2193854 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][S:10][C:11]1[NH:15][C:14]2[CH:16]=[C:17]([Cl:21])C(I)=[CH:19][C:13]=2[N:12]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=1B(O)O.[C:33](=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][P:4]([CH2:9][S:10][C:11]1[NH:15][C:14]2[CH:16]=[C:17]([Cl:21])[C:29]([C:26]3[CH:27]=[CH:28][C:23]([Cl:22])=[C:24]([CH3:33])[CH:25]=3)=[CH:19][C:13]=2[N:12]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 177502352-Chloro-5-methylphenylboronic Acid (contains varying amounts of Anhydride)HCID 58422987(6-Chloro-5-iodo-1H-benzoimidazol-2-ylsulfanylmethyl)-phosphonic acid diethyl ester2×

Product 1

HCID 86657369[6-Chloro-5-(4-chloro-3-methyl-phenyl)-1H-benzoimidazol-2-ylsulfanylmethyl]-phosphonic acid diethyl ester

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of (6-Chloro-5-iodo-1H-benzoimidazol-2-ylsulfanylmethyl)-phosphonic acid diethyl ester (Intermediate 1, 255 mg, 0.55 mmol) in toluene (2 mL) was added 4-chloro-m-tolueneboronic acid (185 mg, 1.1 mmol), tetrakis(triphenylphosphine)palladium(0) (70 mg, 0.061 mmol), and potassium carbonate (305 mg, 2.2 mmol) as a solution in H2O (1 mL). The resulting mixture was heated in a sealed microwave vial at 130° C. for 15 minutes. The reaction was quenched with saturated aqueous ammonium chloride, partitioned between CH2Cl2 and H2O, and filtered through a Celite™ pad. The organic and aqueous layers were separated. The organic layer was dried with MgSO4 and the solvent was removed by rotary evaporation. The residue was purified by flash chromatography (SiO2, 12 g) using a gradient up to 9:1 EtOAc:Hexane to isolate the title compound 12-1.

Workup

  1. customThe reaction was quenched with saturated aqueous ammonium chloride
  2. custompartitioned between CH2Cl2 and H2O
  3. filtrationfiltered through a Celite™ pad
  4. customThe organic and aqueous layers were separated
  5. dry with materialThe organic layer was dried with MgSO4
  6. customthe solvent was removed by rotary evaporation
  7. customThe residue was purified by flash chromatography (SiO2, 12 g)

Sources & evidence

ORD record
ord-13eb8ccc90c74de8a430c4b7d2757912
Source dataset
uspto-grants-2012_12
Patent number
US08329914B2

Reaction notes

Loading…