With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.101691-94-5,4-(Iodomethyl)tetrahydro-2H-pyran,as a common compound, the synthetic route is as follows.
In a round bottom flask under argon was placed tetrahydrofuran (50 mL) and 1,1,1,3,3,3-hexamethyldisilazane (3.21 mL, 15.33 mmol) and it was cooled to -78 C. in a dry ice/acetone bath. To this cooled solution was then added n-butyl lithium (2.5 M solution in hexanes, 5.8 mL, 14.38 mmol) and it was stirred for 15 min at -78 C. To this cooled solution was then added a solution of (3,4-dichloro-phenyl)-acetic acid methyl ester (prepared as in PCT WO 2003/095438 A1, Example 1, 3.00 g, 13.69 mmol) in tetrahydrofuran (40 mL) dropwise. This was then stirred for 10 min at -78 C. then at 0 C. for 45 min which resulted in an amber solution. After such time, the reaction was cooled back to -78 C. and a solution of 4-iodomethyl-tetrahydro-pyran (prepared as in PCT WO 2003/095438 A1, Example 20, 3.71 g, 16.43 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (2.5 mL, 20.54 mmol) was added dropwise at -78 C. The reaction was then allowed to slowly warm to 0 C. and it was stirred for 16 h. After such time, the reaction was diluted with ethyl acetate (500 mL) and washed with a saturated aqueous ammonium chloride solution (1¡Á100 mL) followed by a saturated sodium chloride solution wash (1¡Á100 mL). The organics were dried over sodium sulfate, filtered and then concentrated in vacuo. Flash column chromatography (Merck Silica gel 60, 230-400 mesh, 10% ethyl acetate/hexanes to 20% ethyl acetate/hexanes) afforded 2-(3,4-dichloro-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid methyl ester (2.26 g, 52%) as a gold viscous oil: 1H NMR(300 MHz, CDCl3) delta ppm 1.22-1.47 (m, 3 H, CH2 and CH of CH2), 1.54-1.75 (m, 3 H, CH2 and CH of CH2), 1.96-2.07 (m, 1 H, CH), 3.25-3.36 (m, 2 H, OCH2), 3.64 (t, J=7.4 Hz, 1 H, ArCH), 3.89-3.97 (m, 2 H, OCH2), 7.15 (dd, Jo=8.3 Hz, Jm=2.0 Hz, 1 H, Ar), 7.37-7.42 (m, 2 H, Ar)., 101691-94-5
101691-94-5 4-(Iodomethyl)tetrahydro-2H-pyran 2795507, aTetrahydropyrans compound, is more and more widely used in various.
Reference£º
Patent; Berthel, Steven Joseph; Kester, Robert Francis; Murphy, Douglas Eric; Prins, Thomas Jay; Ruebsam, Frank; Sarabu, Ramakanth; Tran, Chinh Viet; Vourloumis, Dionisios; US2008/21032; (2008); A1;,
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