With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.
To a solution of tert-butyl (3R)-3-(hydroxymethyl)piperazine-l-carboxylate (5.00 g, 23.12 mmol, 1.00 eq) in ethyl acetate (50 mL) and water (50 mL) was added sodium bicarbonate (5.83 g, 69.00 mmol, 3.00 eq) in one portion, then benzyl carbonochloridate (5.94 g, 35.00 mmol, 1.51 eq) was added to the solution slowly with stirring at 0 C for 30 minutes. The resulted solution was stirred at 10 C for 5 hours. The organic layer was separated from the reaction solution, and washed with water (10 mL). The aqueous phase was extracted with ethyl acetate (100 mL). The organic layer was collected and combined, washed with water (30 mL x 3) brine (30 mL), dried over sodium sulfate, concentrated under reduced pressure to give a yellow liquid. The yellow liquid was purified by silica gel column chromatography (Petroleum ether/Ethyl acetate = 3/1 to 1/1) to obtained compound Ol-benzyl-04-tert-butyl (2R)-2-(hydroxymethyl)piperazine- l,4-dicarboxylate (8.00 g, 22.83 mmol, 99% yield) as colorless liquid. 1H-NMR (400MHz, CDCL) d 7.33 – 7.24 (m, 5H), 5.08 (s, 2H), 4.18 (br s, 1H), 3.87 (br s, 2H), 3.57 (br s, 2H), 3.12 – 2.78 (m, 2H), 1.97 (s, 2H), 1.60 – 1.57 (m, 1H), 1.40 (s, 9H)., 278788-66-2
The synthetic route of 278788-66-2 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; ARVINAS OPERATIONS, INC.; YALE UNIVERSITY; CREW, Andrew P.; HORNBERGER, Keith R.; WANG, Jing; DONG, Hanqing; BERLIN, Michael; CREWS, Craig M.; (1213 pag.)WO2019/195609; (2019); A2;,
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