Potassium Carbonate → Tritylolmesartan medoxomil

HRID 52955Notes

Reaction equation

HRID 52955 reaction equation
C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]([C:11]1[N:12]=[C:13]([CH2:27][CH2:28][CH3:29])[NH:14][C:15]=1[C:16]([O:18][CH2:19][C:20]1[O:21][C:22](=[O:26])[O:23][C:24]=1[CH3:25])=[O:17])([CH3:10])[CH3:9].[C:30]([N:49]1[C:53]([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=2[C:60]2[CH:67]=[CH:66][C:63]([CH2:64]Br)=[CH:62][CH:61]=2)=[N:52][N:51]=[N:50]1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CN(C)C(=O)C.C(OCC)(=O)C>[OH:7][C:8]([C:11]1[N:12]=[C:13]([CH2:27][CH2:28][CH3:29])[N:14]([CH2:64][C:63]2[CH:62]=[CH:61][C:60]([C:55]3[CH:56]=[CH:57][CH:58]=[CH:59][C:54]=3[C:53]3[N:49]([C:30]([C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)[C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[N:50]=[N:51][N:52]=3)=[CH:67][CH:66]=2)[C:15]=1[C:16]([O:18][CH2:19][C:20]1[O:21][C:22](=[O:26])[O:23][C:24]=1[CH3:25])=[O:17])([CH3:9])[CH3:10]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 100534615-(4'-(Bromomethyl)(1,1'-biphenyl)-2-yl)-1-trityl-1H-tetraazoleHCID 178440076HCID 178440076, compound

Product 1

HCID 19036162Tritylolmesartan medoxomilYield 49.7%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
60 °C

Procedure

A suspension of 0.97 g of potassium carbonate in 100 ml of N,N-dimethylacetamide was warmed at 60° C., and then a solution of 1.14 g of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate (prepared as described in Preparation 31) and 2.35 g of 4-[2-(trityltetrazol-5-yl)phenyl]benzyl bromide in 50 ml of N,N-dimethylacetamide was added dropwise to the warm suspension, whilst stirring. The reaction mixture was stirred at 60° C. for 3.5 hours, and it was then diluted with ethyl acetate. The ethyl acetate layer was separated, washed with water and dried over anhydrous magnesium sulfate, and then the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel, using a 1:1 by volume mixture of hexane and ethyl acetate as the eluent, to give 1.4 g of the title compound as an amorphous solid. This product was crystallized from diisopropyl ether, to give pure title compound, melting at 98°-99° C. (with decomposition).

Workup

  1. stirringThe reaction mixture was stirred at 60° C. for 3.5 hours
  2. customThe ethyl acetate layer was separated
  3. washwashed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was removed by distillation under reduced pressure
  6. customThe resulting residue was purified by column chromatography through silica gel
  7. additionby volume mixture of hexane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-1a3dd5db65fb43548970d1fd46948b94
Source dataset
uspto-grants-1997_04
Patent number
US05616599

Reaction notes

Loading…