Water → (1-(4-(Azetidin-3-yloxy)-2-methylbenzyl)-4-methylpiperidin-4-yl)methanol

Participants

Reaction Steps

To a solution of 69B (3.10 g, 7.66 mmol) in DCM (100 mL) was added TFA (30 mL) and the reaction mixture was stirred at RT for 2 h. The mixture was transferred to a reparatory funnel and water was added. The aqueous phase was carefully basified with Na2CO3. The organic layer was separated and the basic aqueous layer was extracted ten times with. The combined organic layers were filtered through a phase separator and the solvent was removed by evaporation. The residue was dissolved in a mixture of THF (30 mL) and an aqueous solution of NaOH (1M, 40 mL). The mixture was stirred at RT for 4 h and then the solution was concentrated using a rotavapor. The aqueous residue was extracted several times with DCM. The aqueous layer was diluted with a saturated solution of NaHCO3 and the mixture was further extracted with DCM. The combined organic layers were filtered through a phase separator and the solvent was removed by evaporation. There was obtained 1.65 g (71%) of 69C as an oil. 1H NMR (500 MHz, CDCl3): δ 0.95 (s, 3H), 1.32 (m, 2H), 1.54 (m, 2H), 2.32 (m, 2H), 2.54 (m, 2H), 3.38 (s, 2H), 3.42 (s, 2H), 3.83 (m, 2H), 3.95 (m, 2H), 4.97 (m, 1H), 6.50 (dd, 1H), 6.57 (s, 1H), 7.16 (d, 1H), MS (APCI+) m/z 305 [M+H]+.

Provenance & Evidence