Dimethyl Sulfoxide → (7aR)-2-Chloro-3-methyl-4-(7a-methyl-3,7-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)benzonitrile

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Reaction Steps

To a 2 M CH2Cl2 solution of oxalyl chloride (68 □L, 0.13 mmol) in CH2Cl2 (2 mL) at −78° C. was added DMSO (17□L, 0.25 mmol). After 20 min, a solution of (7R,7aR)-2-chloro-4-(7-hydroxy-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile (58F) (17 mg, 0.06 mmol) in CH2Cl2 (1 mL) was added. After an additional 20 min at −78° C., triethylamine (62 □L, 0.47 mmol) was added, the cold bath was removed, and the reaction mixture was stirred for 20 min. Water was added and the layers were separated. The organic layer was washed with brine then dried (MgSO4), filtered and concentrated. The resulting residue was purified via preparative HPLC (YMC ODS C-18, 100×20 mm, eluting with 30-80% solvent B (A=90% H2O—10% CH3CN—0.1% TFA and B=10% H2O—90% CH3CN—0.1% TFA) over 15 min; Flow rate at 20 mL/min; UV detection at 220 nm) to provide the title compound (6.3 mg) as a white solid. LC/MS m/z 629 [2M+23]+.

Provenance & Evidence