Potassium Carbonate → Telmisartan methyl ester

HRID 1783902Notes

Reaction equation

HRID 1783902 reaction equation
[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[C:11]1[CH:22]=[C:21]([CH3:23])[C:14]2[N:15]=[C:16]([CH2:18][CH2:19][CH3:20])[NH:17][C:13]=2[CH:12]=1.[C:24]([O-])([O-])=O.[K+].[K+].Br[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[C:39]([C:44]([OH:46])=[O:45])=[CH:40][CH:41]=[CH:42][CH:43]=2)=[CH:34][CH:33]=1>[Cl-].C[N+](CCCC)(CCCC)CCCC.C1(C)C=CC=CC=1>[CH3:20][CH2:19][CH2:18][C:16]1[N:17]([CH2:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]3[C:39]([C:44]([O:46][CH3:24])=[O:45])=[CH:40][CH:41]=[CH:42][CH:43]=3)=[CH:34][CH:33]=2)[C:13]2[C:14](=[C:21]([CH3:23])[CH:22]=[C:11]([C:3]3[N:2]([CH3:1])[C:6]4[C:5](=[CH:10][CH:9]=[CH:8][CH:7]=4)[N:4]=3)[CH:12]=2)[N:15]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 97960434'-(Bromomethyl)-(1,1'-biphenyl)-2-carboxylic acidHCID 97964884-Methyl-6-(1-methyl-1H-benzimidazol-2-yl)-2-propyl-1H-benzimidazole

Product 1

HCID 11497808Telmisartan methyl esterYield 72.3%

Reagents, catalysts & solvents 2

HCID 91822Tributylmethylammonium chlorideCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
87.5 °C

Procedure

1,7′-dimethyl-2′-propyl-1H,3′H-[2,5′]bibenzoimidazolyl (BIM) (4 g), Aliquat® 175 (1.36 ml), K2CO3 (8.19 g), and toluene (50 ml) were added to a 250 ml round bottom flask equipped with a magnetic stirring bar and reflux condenser. The mixture was heated to reflux (about 85-90° C.) until a clear brown organic solution was obtained. 4′bromomethyl-biphenyl-2-carboxylic acid (BMBP) methyl ester (4.5 g) in toluene (24 ml) was added to the clear brown organic solution to form a reaction mixture. The reaction mixture was stirred for about 6 hrs then cooled by ice bath and filtered forming a cooled reaction mixture. The cooled reaction mixture was then extracted twice with water (20 ml), dried over MgSO4, and evaporated forming telmisartan methyl ester (5.02 g), which is about a 69% yield.

Workup

  1. customequipped with a magnetic stirring bar
  2. temperaturereflux condenser
  3. temperatureThe mixture was heated
  4. customwas obtained
  5. customto form a reaction mixture
  6. temperaturethen cooled by ice bath
  7. filtrationfiltered
  8. customforming
  9. customa cooled reaction mixture
  10. customThe cooled reaction mixture
  11. extractionwas then extracted twice with water (20 ml)
  12. dry with materialdried over MgSO4
  13. customevaporated

Sources & evidence

ORD record
ord-6e348835439b42cf93ab335a3b32cf69
Source dataset
uspto-grants-2009_03
Patent number
US07501448B2

Reaction notes

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