With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.19752-84-2,Tetrahydro-2H-pyran-3-ol,as a common compound, the synthetic route is as follows.
To a solution of DIAD (2.0 equiv.) and triphenylphosphine (2.0 equiv.) in THF (0.24 M) was added tetrahydro-2H-pyran-3-ol (1.2 equiv.). The mixture was stirred for 10 min. methyl 6-(2,6-difluoro-4-hydroxyphenyl)-5-fluoropicolinate (1.0 equiv.) was added. The mixture was stirred at ambient temperature overnight. Additional triphenylphosphine (2.0 equiv.) and DIAD (2.0 equiv.) were added, and the mixture was stirred overnight. The mixture was concentrated and purified by flash chromatography over silica gel (heptanes:ethyl acetate gradient) to give methyl 6-(2,6-difluoro-4-((tetrahydro-2H-pyran-3-yl)oxy)phenyl)-5-fluoropicolinate in 39% yield. Purification was completed via chiral HPLC (EtOH/heptane)=15/85, 20 mL/min, AD column) to yield (S)-methyl 6-(2,6-difluoro-4-((tetrahydro-2H-pyran-3-yl)oxy)phenyl)-5-fluoropicolinate (18% yield, 99% ee) and (R)-methyl 6-(2,6-difluoro-4-((tetrahydro-2H-pyran-3-yl)oxy)phenyl)-5-fluoropicolinate (18% yield, 99% ee). LC/MS=368.2 (MH+), Rt=0.92 min. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.65 (ddd, J=12.81, 8.51, 4.11 Hz, 1H), 1.78-1.97 (m, 2H), 2.06-2.16 (m, 1H), 3.57-3.67 (m, 2H), 3.72-3.80 (m, 1H), 3.95 (dd, J=11.54, 2.15 Hz, 1H), 3.99-4.01 (m, 3H), 4.32 (dt, J=6.95, 3.37 Hz, 1H), 6.54-6.62 (m, 2H), 7.59-7.67 (m, 1H), 8.19-8.28 (m, 1H)., 19752-84-2
The synthetic route of 19752-84-2 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; Burger, Matthew; Ding, Yu; Han, Wooseok; Nishiguchi, Gisele; Rico, Alice; Simmons, Robert Lowell; Smith, Aaron R.; Tamez, JR., Victoriano; Tanner, Huw; Wan, Lifeng; US2012/225061; (2012); A1;,
Tetrahydropyran – Wikipedia
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