Cesium carbonate → HCID 178440171, compound

HRID 1197583Notes

Reaction equation

HRID 1197583 reaction equation
[CH2:1]([C:4]1[NH:5][C:6]([C:20]([O:22][CH3:23])=[O:21])=[C:7]([N:9]2[CH:13]=[CH:12][CH:11]=[C:10]2[C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[N:8]=1)[CH2:2][CH3:3].C([O-])([O-])=O.[Cs+].[Cs+].C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:37]2[C:41]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[C:48]3[CH:53]=[CH:52][C:51]([CH2:54]Br)=[CH:50][CH:49]=3)=[N:40][N:39]=[N:38]2)C=CC=CC=1>CN(C=O)C>[O:19]=[C:14]([C:10]1[N:9]([C:7]2[N:8]=[C:4]([CH2:1][CH2:2][CH3:3])[N:5]([CH2:54][C:51]3[CH:52]=[CH:53][C:48]([C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=4[C:41]4[NH:37][N:38]=[N:39][N:40]=4)=[CH:49][CH:50]=3)[C:6]=2[C:20]([O:22][CH3:23])=[O:21])[CH:13]=[CH:12][CH:11]=1)[C:15]([F:17])([F:16])[F:18]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 100534615-(4'-(Bromomethyl)(1,1'-biphenyl)-2-yl)-1-trityl-1H-tetraazoleHCID 14962887HCID 14962887, compound

Product 1

HCID 178440171HCID 178440171, compoundYield 96.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Methyl 2-propyl-4-[2-(1-oxo-2,2,2-trifluoroethyl)-1H-pyrrol-1-yl]imidazole-5-carboxylate (15 g, 0.046 mol) from Example 6 was dissolved in DMF (500 mL) and Cs2CO3 (32.9 g, 0.1 mol) added. After 5 minutes, N-triphenylmethyl-5-[4'-(bromomethyl)biphenyl-2-yl]tetrazole (Example 12, 26.9 g, 0.048 mol) was added and the reaction mixture stirred at room temperature for 6 hours. The reaction was filtered to remove insoluble salts and the DMF removed high vacuum. The residue was partitioned between ethyl acetate (150 mL) and water (50 mL). The organic layer was extracted with brine, dried over anhydrous magnesium sulfate, and the solvent evaporated under reduced pressure. Chromatography of the residue on silica gel, eluting with a gradient of ethyl acetate/hexane (1:4) to ethyl acetate/hexane (1:1) afforded 25 g of the title compound in its triphenylmethyl-protected form. The triphenylmethyl protecting group was removed by refluxing in methanol (280 mL) containing 10% aqueous citric acid (28 mL) for 4 hours. The reaction mixture was diluted with water (100 mL) and the milky solution extracted with several times with hexane. The aqueous layer was extracted with ethyl acetate and the combined organic layers extracted with brine. The organic layer was dried over anhydrous magnesium sulfate and the solvent removed under reduced pressure. The residue was recrystallized using Hexane/ethyl acetate (1:1) to afford 13.4 g of the title compound. MS (FAB, thioglycerol) 564(M+1), mp 135°-137° C.

Workup

  1. filtrationThe reaction was filtered
  2. customto remove insoluble salts
  3. customThe residue was partitioned between ethyl acetate (150 mL) and water (50 mL)
  4. extractionThe organic layer was extracted with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent evaporated under reduced pressure
  7. washChromatography of the residue on silica gel, eluting with a gradient of ethyl acetate/hexane (1:4) to ethyl acetate/hexane (1:1)

Sources & evidence

ORD record
ord-40418502051145cb8a47c6975bb05f7b
Source dataset
uspto-grants-1994_01
Patent number
US05276048

Reaction notes

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