Sodium hydride → HCID 71244864, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of above crude cis and trans mixture of 1-benzyl-3-(hydroxymethyl)piperidin-4-ol (2.69 g, 12.16 mmol) in DCM (60 mL) was added DIPEA (3.39 mL, 24.31 mmol) and MsCl (0.947 mL, 12.2 mmol) dropwise at 0° C. The reaction mixture was further stirred for 1.5 h at 0-5° C. and then quenched with saturated aqueous NaHCO3. The aqueous phase was extracted with DCM. The combined organic phases were dried over Na2SO4, filtered and concentrated to afford a mixture of mono- and bi-mesylated compounds. The crude was then dissolved in THF (250 mL) and added NaH (1.05 g, 43.8 mmol, 60% in mineral oil) portionwise at room temperature. After being stirred for 40 min at room temperature, the reaction mixture was then heated to 65° C. for 4.5 h. The reaction mixture was cooled to room temperature, then quenched with water and concentrated in vacuo. The residue was dissolved in EtOAc, washed with saturated aqueous NH4Cl, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (0-100% EtOAc/heptanes) to provide racemic (cis)-3-benzyl-7-oxa-3-azabicyclo[4.2.0]octane as a colorless oil. 1H NMR (400 MHz, CD2Cl2) δ ppm 7.32-7.41 (m, 5H), 4.97 (ddd, J=3.03, 4.42, 6.19 Hz, 1H), 4.68 (t, J=5.68 Hz, 1H), 4.07-4.13 (m, 1H), 3.53-3.60 (m, 2H), 2.90-2.98 (m, 1H), 2.82-2.90 (m, 1H), 2.52-2.59 (m, 2H), 2.49 (dd, J=6.32, 11.37 Hz, 1H), 1.83-1.87 (m, 2H).

Provenance & Evidence