Water → HCID 67277501, compound

Participants

Reaction Conditions

Reaction Steps

An amount of 2.9 g (7.0 mmol) of 2-(tert-butyl-dimethyl-silanyl)-4-(2,3-difluoro-benzyl)-imidazole-1-sulfonic acid dimethylamide was dissolved in 30 ml tetrahydrofuran and added drop-wise to a freshly prepared solution of lithium diisopropylamide in tetrahydrofuran (from 6.54 ml 1.6M BuLi and 1.06 g diisopropylamine). After stirring for 1 h at −75° C., 1.14 g (8.0 mmol) methyl iodide was added, and stirring was continued overnight at ambient temperature. Water was added to quench the reaction. The aqueous phase was extracted with ethyl acetate (3 times) and the combined organic extracts were dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (silica gel, hexanes/ethyl acetate 4:1) to yield 2.47 g of rac-2-(tert-butyl-dimethyl-silanyl)-4-[1-(2,3-difluoro-phenyl)-ethyl]-imidazole-1-sulfonic acid dimethylamide (MS (ISP): 430.3 ((M+H)+.), light yellow oil). This material was separated by chiral column chromatography (Chiral OD, isopropanol/heptane=2:98) to yield 0.785 g (26%) of (+)-2-(tert-butyl-dimethyl-silanyl)-4-[1-(2,3-difluoro-phenyl)-ethyl]-imidazole-1-sulfonic acid dimethylamide and 0.946 g (32%) of (+)-2-(tert-butyl-dimethyl-silanyl)-4-[1-(2,3-difluoro-phenyl)-ethyl]-imidazole-1-sulfonic acid dimethylamide.

Provenance & Evidence