With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.208167-83-3,tert-Butyl 4-(2-chloroethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.
To a solution of tert-butyl 4-(2-chloroethyl)piperazine- l-carboxylate (1.00 g, 4.02 mmol, 1.00 eq), 4-benzyloxyphenol (965 mg, 4.82 mmol, 1.20 eq) in N,N-dimethylformamide (20 mL) was added cesium carbonate (1.57 g, 4.82 mmol, 1.20 eq) and potassium iodide (66 mg, 0.4 mmol, 0.10 eq) under nitrogen. The reaction was stirred at 80 C for 10 hours. TLC (Petroleum ether/Ethyl acetate = 3/1) and LC/MS showed most of the starting material was consumed. Water (100 mL) was added to the mixture, and the resulting mixture was extracted with ethyl acetate (50 mL x 3). The combined organic phase was washed with brine (80 mL), dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 50/1 to 3/1) to provide tert- butyl 4-[2-(4-benzyloxyphenoxy)ethyl]piperazine-l-carboxylate (1.4 g, 3.39 mmol, 84% yield) as a colorless oil. 1H NMR (400MHz, CDC13) delta 7.46 – 7.29 (m, 5H), 6.95 – 6.88 (m, 2H), 6.88 – 6.81 (m, 2H), 5.02 (s, 2H), 4.07 (t, = 5.8 Hz, 2H), 3.51 – 3.42 (m, 4H), 2.80 (t, = 5.8 Hz, 2H), 2.56 – 2.48 (m, 4H), 1.47 (s, 9H).
208167-83-3, As the paragraph descriping shows that 208167-83-3 is playing an increasingly important role.
Reference：
Patent; ARVINAS, INC.; QIAN, Yimin; CREW, Andrew, P.; CREWS, Craig, M.; DONG, Hanqing; HORNBERGER, Keith, R.; WANG, Jing; (606 pag.)WO2018/140809; (2018); A1;,
Piperazine – Wikipedia
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