Uses
3-Acetyl-1-Boc-pyrrolidine is a boc protected reagent that is used for selective inhibitors of H. influenzae TrmD that mimic tRNA interaction by inducing TrmD lid domain ordering.
Synthesis
The general procedure for the synthesis of N-Boc-3-acetylpyrrolidine from tert-butyl 3-(methoxy(methyl)carbamoyl)pyrrolidine-1-carboxylate and methylmagnesium bromide was as follows: tert-butyl 3-(methoxy(methyl)carbamoyl)pyrrolidine-1-carboxylate (4.0 g, 15.50 mmol) was dissolved in THF (70 ml) at 0 °C and under nitrogen protection and stirred. . 3M methylmagnesium bromide ether solution (26 ml, 78 mmol) was added slowly dropwise, keeping the reaction temperature at 0 °C. After the dropwise addition, the reaction mixture was continued to be stirred at 0°C for 30 minutes. Subsequently, the reaction mixture was slowly poured into saturated ammonium chloride solution (1 L) to quench the reaction and extracted with ethyl acetate (2 x 200 ml). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the crude product tert-butyl 3-acetylpyrrolidine-1-carboxylate (3.0 g, 14.08 mmol), which was used directly in the subsequent reaction without further purification. The product was analyzed by LCMS (Method A) with a retention time of 3.83 min, and the mass spectrum (ES+) showed m/z of 157.89 (M-56).1H NMR (400 MHz, DMSO-d6) δ ppm: 3.77-3.40 (m, 2H), 3.22-3.25 (m, 3H), 2.17 (s, 3H), 2.03- 2.11 (m, 1H), 1.85-1.94 (m, 1H), 1.39 (s, 9H).
References
[1] Journal of Organic Chemistry, 2009, vol. 74, # 5, p. 1932 - 1938
[2] Patent: WO2010/51245, 2010, A1. Location in patent: Page/Page column 53
[3] Patent: US2010/298334, 2010, A1. Location in patent: Page/Page column 71-72
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 18, p. 7278 - 7288
[5] Patent: WO2017/103614, 2017, A1. Location in patent: Page/Page column 76; 78
