With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.3970-68-1,4-Methylpiperidin-4-ol,as a common compound, the synthetic route is as follows.
To a solution of (S) -1-phenylethyl 2 -bromo- 2-phenylacetate (0.464 g, 1.45 mmol) in THF (8 mL) was added triethylamine (0.61 mL, 4.35 mmol), followed by tetrabutylammonium iodide (0.215 g, 0.58 mmol) . The reaction mixture was stirred at room temperature for 5 minutes and then a solution of 4- methyl-4-hydroxypiperidine (0.251 g, 2.18 mmol) in THF (2 mL) was added. The mixture was stirred for 1 hour at room temperature and then it was heated at 55-60 0C (oil bath temperature) for 4 hours. The cooled reaction mixture was then diluted with ethyl acetate (30 mL) , washed (H2O x2 , brine), dried (MgSO4), filtered and concentrated. The residue was purified by silica gel chromatography (0-60% ethyl acetate-hexane) to provide first the (S, R) -isomer of the title compound (0.306 g, 60%) as a white solid and then the corresponding (S, S)- isomer (0.120 g, 23%), also as a white solid. (S, R)- isomer: 1H NMR (CD3OD) 5 7.51-7.45 (m, 2H), 7.41-7.25 (m, 8H), 5.85 (q, ,7=6.6 Hz, IH) , 4.05 (s, IH), 2.56-2.45 (m, 2H), 2,41-2.29 (m, 2H), 1.71-1.49 (m, 4H) , 1.38 (d, J=6.6 Hz, 3H), 1.18 (s, 3H) . LCMS: Anal. Calcd. for C22H27NO3: 353; found: 354 (M+H) + . (S, S) -isomer : 1H NMR (CD3OD) 6 7.41-7.30 (m, 5H) , 7.20-7.14 (m, 3H), 7.06-7.0096 (m, 2H), 5.85 (q, J=6,6 Hz, IH), 4.06 (s, IH), 2.70-2.60 (m, IH), 2.51 (dt, J=6.6 , 3.3 Hz, IH), 2.44-2.31 (ra, 2H), 1.75-1.65 (m, IH) , 1.65-1.54 (m, 3H), 1.50 (d, <;J=6.8 Hz, 3H), 1.20 (s, 3H) . LCMS: Anal. Calcd. for C22H27NO3: 353; found: 354 (M+H)+. 3970-68-1, As the paragraph descriping shows that 3970-68-1 is playing an increasingly important role.
Reference£º
Patent; BRISTOL-MYERS SQUIBB COMPANY; LAVOIE, Rico; BENDER, John A.; BACHAND, Carol; RUEDIGER, Edward H.; KADOW, John F.; WO2010/120621; (2010); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem