With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1768-64-5,4-Chlorotetrahydropyran,as a common compound, the synthetic route is as follows.
To a vigorously stirred suspension of Mg (1.76 g, 72.8 mmol) turnings and iodine (46.1 mg, 0.182 mmol) in THF (2 mL) under N2 was added 1,2-dibromoethane (68.3 mg, 0.364 mmol) and 10% of a solution of 4-chlorotetrahydro-2H-pyran (4.4 g, 36.4 mmol) in THF (18 mL). Themixture was heated to 60C and as the reaction mixture turned clear and Grignard initiatedtook place, the remainder of the solution of 4-chlorotetrahydro-2H-pyran in THF was added slowly over 30 mm. The reaction mixture was stirred at 65C for 2h to give a solution of (tetrahydro2H-pyran-4-yl)magnesium chloride in THF (-2M). The Grignard solution was used without any further purification. The solution of 36-4 (800 mg, 2.06 mmol) in THF (150 mL) under N2 wasadded to Grignard reagent at 15C in one portion. After stirring at 15C for 2 mm, the mixture was quenched by 200 mL of sat.NH4C1 and extracted with 200 mL of EtOAc. The separated organic phase was washed with 200 mL of brine, dried over Na2504, filtered and concentrated. The residue was purified by Combi-flash (0%-30% of EtOAc in PE/DCM(v/v=1/1)) to afford 36-5 (550 mg, 56%) as off-white solid, and 50 mg of 36-5 was delivered. ?H NMR (400 MHz,CDC13) 5.32-5.25 (m, 1H), 4.06-3.96 (m, 2H), 3.42-3.29 (m, 3H), 2.39-2.33 (m, 1H), 2.07-1.79(m, 6H), 1.77-1.60 (m, 7H), 1.5 1-1.38 (m, 1OH), 1.35-1.21 (m, 4H), 1.16-1.01 (m, 8H), 0.97-0.90(m, 4H), 0.85 (t, J = 7.4 Hz, 3H), 0.71-0.66 (m, 3H). LCMS Rt = 1.212 mm in 2 mmchromatography, 30-9OAB_2MIN_E.M, MS ESI calcd. for C31H5102 [M+H-H2Oj 455, found455., 1768-64-5
As the paragraph descriping shows that 1768-64-5 is playing an increasingly important role.
Reference£º
Patent; SAGE THERAPEUTICS, INC.; SALITURO, Francesco, G.; ROBICHAUD, Albert, Jean; MARTINEZ BOTELLA, Gabriel; HARRISON, Boyd, L.; (157 pag.)WO2017/7840; (2017); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics