4-Toluenesulfonyl chloride → Azilsartan Medoxomil

HRID 254442Notes

Reaction equation

HRID 254442 reaction equation
[CH2:1]([O:3][C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]3[NH:26][C:25](=[O:27])[O:24][N:23]=3)=[CH:12][CH:11]=2)[C:7]2[C:28]([C:32]([OH:34])=[O:33])=[CH:29][CH:30]=[CH:31][C:6]=2[N:5]=1)[CH3:2].O[CH2:36][C:37]1[O:38][C:39](=[O:43])[O:40][C:41]=1[CH3:42].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.O.CC(C)=O>[CH2:1]([O:3][C:4]1[N:8]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]3[NH:26][C:25](=[O:27])[O:24][N:23]=3)=[CH:14][CH:15]=2)[C:7]2[C:28]([C:32]([O:34][CH2:36][C:37]3[O:38][C:39](=[O:43])[O:40][C:41]=3[CH3:42])=[O:33])=[CH:29][CH:30]=[CH:31][C:6]=2[N:5]=1)[CH3:2]

Participants

8

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 11430Potassium CarbonateHCID 105108784-(Hydroxymethyl)-5-methyl-1,3-dioxol-2-oneHCID 135415867Azilsartan

Product 1

HCID 135409642Azilsartan MedoxomilYield 95%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of 2-ethoxy-1-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid (9.0 g) and 4-hydroxymethyl-5-methyl-1,3-dioxol-2-one (3.08 g) in N,N-dimethylacetamide (100 mL) were added p-toluenesulfonyl chloride (4.13 g), N,N-dimethylaminopyridine (0.48 g) and potassium carbonate (3.54 g) under ice-cooling and the mixture was stirred at about 10° C. for 3 hrs. After adjusting the pH of the mixture to about 5, the mixture was crystallized by adding water (72 mL) to give crystals as a solvate. The isolated crystals were suspended in a mixture of water (63 mL) and acetone (27 mL) and the suspension was stirred at about 35° C. for 2 hrs. After stirring under ice-cooling for 2 hrs, the crystals were collected by filtration and the crystals were washed with water (18 mL) and dried under reduced pressure at 40° C. to give the title compound (10.6 g, 95%).

Workup

  1. temperaturecooling
  2. customthe mixture was crystallized
  3. additionby adding water (72 mL)
  4. customto give crystals as a solvate
  5. stirringthe suspension was stirred at about 35° C. for 2 hrs
  6. stirringAfter stirring under ice-
  7. temperaturecooling for 2 hrs
  8. filtrationthe crystals were collected by filtration
  9. washthe crystals were washed with water (18 mL)
  10. customdried under reduced pressure at 40° C.

Sources & evidence

ORD record
ord-dd936233f3dd415481663452159e4b27
Source dataset
uspto-grants-2011_01
Patent number
US07875637B2

Reaction notes

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