tert-butyl 2-(Methylsulfonyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate

white solid

Tert-butyl 2-(Methylsulfonyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate is an important organic reagent that can be used as a building block for the synthesis of many organic compounds, such as 2-(methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole. It is an important  intermediate of Omarigliptin.

Tert-butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate (3.5 g, 16.7 mmol) was dissolved in tetrahydrofuran (35 ml), and sodium hydride (1.0 g, 60%, 25.4 mmol) was added at 0°C, followed by reaction for 30 min. Methylsulfonyl chloride (2.9 g, 25.4 mmol) was added, followed by a reaction for 1 hour. The reaction was quenched by the addition of water (10 ml) to the reaction solution, which was extracted with ethyl acetate (50 ml*2). The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether/ethyl acetate (v/v) = 1:1), to obtain tert-butyl 2-(Methylsulfonyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate (2.1 g, yield 44%).

[1] Patent: EP3159344, 2017, A1. Location in patent: Paragraph 0096; 0132; 0133
[2] Patent: TW2017/8222, 2017, A. Location in patent: Page/Page column 54; 55
[3] Patent: TW2017/8223, 2017, A. Location in patent: Page/Page column 43
[4] Patent: WO2011/103256, 2011, A1. Location in patent: Page/Page column 55
[5] Patent: WO2011/146358, 2011, A1. Location in patent: Page/Page column 61