Sulfuric Acid → 4-Difluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-carboxylic acid

HRID 558637Notes

Reaction equation

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

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 4-difluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-carboxylic acid ethyl ester (6.0 g, 15.6 mmol), potassium hydroxide 14 g (0.25 mmol) in water (62.5 ml) and methanol (125 ml) was stirred at room temperature for 2 h and at 60° C. for 1 h, cooled (ice-water), and 3N sulfuric acid (90 ml) was added. The formed precipitate (4.32 g) was collected by filtration, acetic acid (65 ml) was added and the stirred solution was heated under reflux conditions for 1 h. The reaction mixture was evaporated, ethyl acetate (30 ml) was added and the mixture was stirred for 30 min at 0° C. The precipitate was collected by filtration and dried to yield 4-difluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-carboxylic acid (2.15 g, 39%) as a yellow solid. MS (ISN) 356.0 [(M−H)−]; mp 238° C.

Workup

additionwas added
filtrationThe formed precipitate (4.32 g) was collected by filtration, acetic acid (65 ml)
additionwas added
temperaturethe stirred solution was heated under reflux conditions for 1 h
customThe reaction mixture was evaporated
additionethyl acetate (30 ml) was added
stirringthe mixture was stirred for 30 min at 0° C
filtrationThe precipitate was collected by filtration
customdried

Sources & evidence

ORD record: ord-8194150d2261431c8557aedc980ef9fe
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063048B2

Reaction notes

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