Trityl chloride → HCID 71315330, compound

HRID 1427703Notes

Reaction equation

HRID 1427703 reaction equation
[C:1]([C:4]1[N:5]=[C:6]([CH2:30][CH2:31][CH3:32])[N:7]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]3[NH:29][N:28]=[N:27][N:26]=3)=[CH:15][CH:14]=2)[C:8]=1[C:9]([OH:11])=[O:10])([CH3:3])=[CH2:2].C1CCN2C(=NCCC2)CC1.[C:44]1([C:50](Cl)([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.Cl[CH2:65][C:66]1[O:67][C:68](=[O:72])[O:69][C:70]=1[CH3:71]>CC(C)=O>[C:1]([C:4]1[N:5]=[C:6]([CH2:30][CH2:31][CH3:32])[N:7]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]3[N:26]=[N:27][N:28]([C:50]([C:57]4[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=4)([C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)[C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[N:29]=3)=[CH:17][CH:18]=2)[C:8]=1[C:9]([O:11][CH2:65][C:66]1[O:67][C:68](=[O:72])[O:69][C:70]=1[CH3:71])=[O:10])([CH3:3])=[CH2:2]

Participants

6

Reactant 4

HCID 6456Trityl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 98555184-(Chloromethyl)-5-methyl-1,3-dioxol-2-one2×HCID 178440065HCID 178440065, compound2×

Product 1

HCID 71315330HCID 71315330, compoundYield 128.8%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
50 °C

Procedure

4-Isopropenyl-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole-5-carboxylic acid [olmesartan dehydrate, compound 34b described in J. Med. Chem., 39, 323-338 (1996)] (139.36 g), acetone (1022.3 ml), 1,8-diazabicyclo[5,4,0]-7-undecene [DBU] (154.3 g) and triphenylmethyl chloride [TPC] (109.6 g) were mixed and the mixture was stirred at 48 to 52° C. for 5 hours. The reaction mixture was cooled to 20° C. and 4-chloromethyl-5-methyl-1,3-dioxol-2-one [DMDO-Cl] (99.1 g) was added, and the reaction mixture was stirred at 48 to 52° C. for 2.5 hours and then at 55 to 58° C. for 1.5 hours. 1,8-Diazabicyclo[5,4,0]-7-undecene [DBU] (45.4 g) and 4-chloromethyl-5-methyl-1,3-dioxol-2-one [DMDO-Cl] (49.5 g) were added to the reaction mixture and the reaction mixture was stirred at 56 to 57° C. for 5 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (3000 ml) and water (1000 ml) and extracted 4 times. The obtained organic layer was concentrated under reduced pressure to obtain 327.83 g of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-isopropenyl-2-propyl-1-[[2′-[2-(triphenylmethyl)-2H-tetrazol-5-yl]biphenyl-4-yl] methyl]imidazole-5-carboxylate [crude trityl olmesartan medoxomil dehydrate] as an oil.

Workup

  1. temperatureThe reaction mixture was cooled to 20° C.
  2. stirringthe reaction mixture was stirred at 48 to 52° C. for 2.5 hours
  3. waitat 55 to 58° C. for 1.5 hours
  4. stirringthe reaction mixture was stirred at 56 to 57° C. for 5 hours
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. dissolutionthe residue was dissolved in ethyl acetate (3000 ml)
  7. extractionwater (1000 ml) and extracted 4 times
  8. concentrationThe obtained organic layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-b27944c90531406eb5d7fd34175982f4
Source dataset
uspto-grants-2015_01
Patent number
US08933241B2

Reaction notes

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