Carbon Dioxide → (R)-5-(4-bromo-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid

Temperature

-40 °C

A solution of (R)-3-(4-bromo-benzyl)-1-(3,5-dichloro-phenyl)-5-iodo-3-methyl-1H-imidazo[1,2-a]imidazol-2-one (4.5 g, 7.8 mmol) in THF (50 mL) was cooled to −40° C. To this was slowly added isopropyl magnesium bromide (1M in THF, 15.6 mL, 15.6 mmol) over 30 min. The reaction mixture was stirred at −40° C. for 1 h and then CO2 gas passed through the solution for 1 h. The reaction mixture was concentrated under reduced pressure and diluted with water. The mixture was acidified with 1N HCl and extracted with CH2Cl2 (3×100 mL). The combined extracts were washed with water, brine and dried with MgSO4. The mixture was filtered and concentrated in vacuo. The residue was dissolved in toluene (40 mL) and hexane was added (100 mL). The resulting precipitate was filtered and washed with hexane to afford 2.6 g of (R)-5-(4-bromo-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid as a purple solid, m/z 495.5 [M+]+.

1. customover 30 min
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. additiondiluted with water
4. extractionextracted with CH2Cl2 (3×100 mL)
5. washThe combined extracts were washed with water, brine
6. dry with materialdried with MgSO4
7. filtrationThe mixture was filtered
8. concentrationconcentrated in vacuo
9. dissolutionThe residue was dissolved in toluene (40 mL)
10. additionhexane was added (100 mL)
11. filtrationThe resulting precipitate was filtered
12. washwashed with hexane

ORD record

ord-e89b28c3b15345999c09d47b8e3dd22d

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08552205B2