3,4-dihydro-2H-pyran → Methyl 4-bromo-3-(tetrahydropyran-2-yloxy)benzoate

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Reaction Steps

The title compound was prepared by adapting the method reported by Kita et al.[Kita, 1994] To a solution of methyl 4-bromo-3-hydroxybenzoate (4.0 g, 17.31 mmol) in anhydrous CH2Cl2 (30 mL) was added 3,4-dihydro-2H-pyran (3.95 mL, 43.28 mmol) and p-toluenesulfonic acid (0.01 g, 0.17 mmol) at 0° C. The mixture was stirred at this temperature for 90 min, warmed to room temperature and quenched with saturated NaHCO3 solution (50 mL). The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The pale yellow residue was purified by flash column chromatography [SiO2, Et2O/n-hexane (4:6)] affording a colourless oil. The oil solidified on standing at room temperature to give methyl 4-bromo-3-(tetrahydropyran-2-yloxy)benzoate as colourless needles (4.12 g, 76%); δH (270 MHz, CDCl3) 1.59-1.77 (m, 3H), 1.86-2.13 (m, 3H), 3.6-3.64 (m, 1H), 3.8-3.85 (m, 1H), 3.88 (s, 3H), 5.6-5.62 (m, 1H), 7.52 (dd, J=8.2, 1.7, 1H), 7.59 (d, J=8.4, 1H), 7.76 (d, J=2.0, 1H); LRMS (FAB+) m/z (rel. intensity) 316.9 (30, [C13H1581BrO4+H]), 314.9 (47, [C13H1579BrO4+H]; LC-MS (APCI+):tR=1.48 min, m/z 334.13 (C13H1581BrO4+H3O+), 332.11 (C13H1579BrO4+H3O+); HPLC: tR=3.21 min (98%); HRMS (FAB+) Found 317.02290; C13H1681BrO4 requires 317.02115.

Provenance & Evidence