With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.25637-16-5,4-Bromotetrahydropyran,as a common compound, the synthetic route is as follows.
25637-16-5, Step 1: (4-Fluorophenyl)(tetrahydro-2H-pyran-4-yl)methanolTo a 40 mL vial containing magnesium (0.39 g, 16.1 mmol) in THF (15 mL) was slowly added 4-bromotetrahydro-2H-pyran (PharmaBlock, 1.8 mL, 16.1 mmol) coolingin a water bath as needed. The resulting reaction mixture was stirred at room temperature for 1.5 h and then cooled in a water bath. 4-Fluorobenzaldehyde (Aldrich, 1.2 mL, 10.7 mmol) was added slowly. The resulting orange reaction mixture was removed from the water bath and quenched with sat. NH4C1 after 10 mm. 10% LiC1 solution was added and the mixture was extracted with Et20 (2x). The organic layer was dried over MgSO4,filtered and concentrated. The residue was purified using ISCO silica gel chromatography (80 g column, gradient from 0% to 50% EtOAc/hexanes) to give the title compound (1.12 g, 33%) as a colorless oil. ?H NMR (500 MHz, CDC13) oe 7.31 – 7.27 (m, 2H), 7.08 – 7.02 (m, 2H), 4.37 (dd, J=7.7, 2.4 Hz, 1H), 4.06 – 3.99 (m, 1H), 3.94 – 3.87 (m, 1H), 3.37 (td,J=11.9, 2.2 Hz, 1H), 3.29 (td,J=11.8, 2.3 Hz, 1H), 1.94- 1.87 (m, 2H),1.81 (tdt, J=1 1.6, 7.7, 3.8 Hz, 1H), 1.45 (qd, J=12.3, 4.7 Hz, 1H), 1.36 – 1.27 (m, 1H),1.16 (ddq, J=13.2, 3.9, 2.0 Hz, 1H); LCMS (M+H-H20) = 193.1; HPLC RT = 1.65 mill(Column: Chromolith ODS S5 4.6 x 50 mm; Mobile Phase A: 10:90 MeOH:water with0.1% TFA; Mobile Phase B: 90:10 MeOH :water with 0.1% TFA; Temperature: 40 C;Gradient: 0-100% B over 4 mm; Flow: 4 mL/min).
The synthetic route of 25637-16-5 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; BRISTOL-MYERS SQUIBB COMPANY; NORRIS, Derek J.; DELUCCA, George V.; GAVAI, Ashvinikumar V.; QUESNELLE, Claude A.; GILL, Patrice; O’MALLEY, Daniel; VACCARO, Wayne; LEE, Francis Y.; DEBENEDETTO, Mikkel V.; DEGNAN, Andrew P.; FANG, Haiquan; HILL, Matthew D.; HUANG, Hong; SCHMITZ, William D.; STARRETT, JR, John E.; HAN, Wen-Ching; TOKARSKI, John S.; MANDAL, Sunil Kumar; WO2015/100282; (2015); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics