Hydrochloric Acid → (R)-6-methyl-1-tosyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one

Participants

Reaction Conditions

Reaction Steps

To tert-butyl 2-((R)-1-((S)-1,1-dimethylethylsulfinamido)ethyl)-1-tosyl-1H-pyrrole-3-carboxylate (287b, 0.55 g, 1.17 mmol) in 4 mL of dioxane under N2 was added hydrogen chloride (Aldrich, St. Louis, Mo.; 4.40 ml of 4.0 M solution in 1,4-dioxane, 17.60 mmol). The homogeneous reaction was sealed and allowed to stir overnight. The reaction was concentrated in vacuo to give a foam. This material was treated with 3 mL DCM and TFA (Aldrich, St. Louis, Mo.; 2.62 mL, 35.2 mmol) and fitted with a drying tube. After 5 h, the stir bar was removed and the reaction was concentrated in vacuo and placed on hood pump overnight, to give a light yellow solid. The solid was treated with 5 mL DCM and 5 mL DMF and cooled to 0° C. DIEA (Aldrich, 1.23 mL, 7.04 mmol) was added dropwise via syringe to give a solution, and PyBoP (Aldrich, 0.73 g, 1.41 mmol) was added in one portion. The ice bath was removed and the reaction warmed to RT. After 1 h, the reaction was treated with ice and saturated aq. NaHCO3. The reaction was partitioned between saturated aq. NaHCO3 and Et2O (slightly cloudy). The aq. layer was extracted 1× Et2O, and the combined organic layers were washed with water 2 times, saturated aq. NaCl once, and the organics (rinsed some undissolved solid into organics from sep funnel with DCM) were dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography (40 g ISCO gold column) using 0-100% EtOAc/hexanes. The product-containing fractions were concentrated to afford (R)-6-methyl-1-tosyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (287c; 0.194 g, 0.67 mmol, 57% yield) as a white foam. 1H NMR (400 MHz, CDCl3) δ ppm 7.74 (2H, d, J=8.4 Hz), 7.35 (2H, d, J=8.2 Hz), 7.16 (1H, d, J=3.1 Hz), 6.48 (1H, d, J=3.1 Hz), 5.76 (1H, br. s.), 4.68 (1H, q, J=6.6 Hz), 2.45 (3H, s), 1.62 (3H, d, J=6.7 Hz). m/z (ESI, +ve) 291.0 (M+H)+.

Provenance & Evidence