4-Toluenesulfonyl chloride → HCID 69022230, compound

Participants

Reaction Steps

To a solution of (2S,3S)-3-(tert-butyldimethylsilanyloxy)-2-hydroxymethyl-2-methylpyrrolidine-1-carboxylic acid (3-chloro-4-cyano-2-methyl-phenyl)-amide (3D) (140 mg, 0.320 mmol) in THF (3 mL) at 0° C. was added a 1 M solution of potassium tert-butoxide in THF (1.12 mL, 1.12 mmol) followed by a solution of p-toluenesulfonyl chloride (152 mg, 0.800 mmol) in THF (1 mL). After 10 min, additional potassium tert-butoxide (200 μL) and p-toluenesulfonyl chloride (5 mg) were added. After another 10 min, additional potassium tert-butoxide (500 μL) was added and the reaction stirred for 2 h. The reaction was diluted with water and EtOAc and the layers were separated. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated and purified via preparative HPLC (Luna C-18, 100×21.2 mm, eluting with 60-100% solvent B (A=90% H2O-10% MeOH-0.1% TFA and B=10% H2O-90% MeOH-0.1% TFA) over 12 min; Flow rate at 20 mL/min; UV detection at 220 nm) to provide compound 3E (8.0 mg, LC/MS m/z 420 [M+H]+), and (7S,7aS)-2-chloro-4-(7-hydroxy-7a-methyl-3-oxo-hexahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile (54.0 mg, LC/MS m/z 420 [M+H]+).

Provenance & Evidence