Water → 4-Trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-carboxylic acid

HRID 1784558Notes

Reaction equation

HRID 1784558 reaction equation
C([O:3][C:4]([C:6]1[N:7]=[CH:8][N:9]2[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][C:12]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[N:11][C:10]=12)=[O:5])C.[OH-].[K+].O>C(O)(=O)C>[F:17][C:15]([F:16])([F:18])[C:14]1[N:9]2[CH:8]=[N:7][C:6]([C:4]([OH:5])=[O:3])=[C:10]2[N:11]=[C:12]([C:19]2[CH:20]=[CH:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=2)[CH:13]=1

Participants

5

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 866080034-Trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-carboxylic acid ethyl ester

Product 1

HCID 866080044-Trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-carboxylic acidYield 37%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 4-trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-carboxylic acid ethyl ester (5.6 g, 13.9 mmol), 2M potassium hydroxide solution (111 ml) and water (55 ml) was stirred at room temperature for 5 h, cooled (ice-water), and acetic acid (30 ml) was added. The mixture was evaporated, acetic acid (150 ml) was added and the stirred solution was heated under reflux conditions for 20 min. The reaction mixture was evaporated, water (150 ml) was added followed by extraction with ethyl acetate (2×300 ml). The combined organic layers were washed with brine (2×150 ml), dried (MgSO4) and evaporated. The crude product was further purified by cholumn chromatography on silica gel (ethyl acetate/heptane 1:1) to yield 4-trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-carboxylic acid (1.93 g, 37%) as a yellow solid. MS (ISN) 374.3 [(M−H)−]; mp 231° C.

Workup

  1. additionwas added
  2. customThe mixture was evaporated
  3. additionacetic acid (150 ml) was added
  4. temperaturethe stirred solution was heated under reflux conditions for 20 min
  5. customThe reaction mixture was evaporated
  6. additionwater (150 ml) was added
  7. extractionfollowed by extraction with ethyl acetate (2×300 ml)
  8. washThe combined organic layers were washed with brine (2×150 ml)
  9. dry with materialdried (MgSO4)
  10. customevaporated
  11. customThe crude product was further purified by cholumn chromatography on silica gel (ethyl acetate/heptane 1:1)

Sources & evidence

ORD record
ord-eb2753a79918404f93554e287a063795
Source dataset
uspto-grants-2009_03
Patent number
US07504404B2

Reaction notes

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