Acetic Acid → ethyl 1-(4-chlorophenyl)-2-propyl-1H-imidazole-4-carboxylate

HRID 75485Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[NH:13])[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+].Br[CH2:20][C:21](=O)[C:22]([O:24][CH2:25][CH3:26])=[O:23].CC(O)=O>CC(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:20]=[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[N:13]=[C:9]2[CH2:10][CH2:11][CH3:12])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of N-(4-chlorophenyl)butyrimidamide (compound 3, 3.5 g, 17.80 mmol), NaHCO3 (3.14 g, 37.38 mmol) in i-PrOH was added ethyl bromopyruvate (compound 4, 4.7 mL, 37.38 mmol) under N2. The reaction mixture was stirred at 85° C. for 72 hrs, then added AcOH (15 mL). After 4 hrs, the mixture was concentrated under reduced pressure. The residue was diluted with H2O, and extracted with CH2Cl2. The organic layer was washed with saturated NaHCO3 and 1N-HCl solution, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (Biotage Isolera™ FLASH Purification System was used for normal phase column chromatography with EtOAc and hexane) to provide the title compound (1.28 g, 25%) as a brown oil.

Workup

waitAfter 4 hrs
concentrationthe mixture was concentrated under reduced pressure
additionThe residue was diluted with H2O
extractionextracted with CH2Cl2
washThe organic layer was washed with saturated NaHCO3 and 1N-HCl solution
dry with materialdried over anhydrous MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by flash column chromatography (Biotage Isolera™ FLASH Purification System was used for normal phase column chromatography with EtOAc and hexane)

Sources & evidence

ORD record: ord-2cd7dc2d80d24989bc3361bc4bc8049d
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835436B2

Reaction notes

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