Methyl iodide → 4-(4-Methoxypiperidin-1-yl)benzoic acid

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Reaction Steps

170 mg (0.77 mmol) of 4-(4-hydroxy-piperidin-1-yl)-benzoic acid (reference example 113d) were dissolved in 3 ml of THF and 3 ml of DMSO, 120 mg (1.1 equiv) of methyl iodide and 68 mg (1.69 mmol) of NaH were added and stirred 16 h at room temperature. The mixture was poured into brine and extracted with DCM (3×) aqueous phase acidified with HCl to pH 1 and extracted again with DCM (3×). The combined organic extracts were washed with brine, dried with Na2SO4, filtered and evaporated. TLC (DCM/MeOH 10%) showed a mixture of the starting material (Rf˜0.5) and a new product with Rf˜0.6. The two were separated by chromatography on silica with DCM/MeOH (0-10%) as a mobile phase to give 60 mg of the title compound. 1H NMR (CDCl3): d 7.95 (d, 2H), 6.87 (d, 2H), 3.68 (m, 2H), 3.63 (m, 1H), 3.38 (s, 3H), 3.14 (m, 2H), 1.98 (m, 2H), 1.68 (m, 2H). MS (ion spray) m/z 236 (M+H)+.

Provenance & Evidence