Furan, 2-(bromomethyl)tetrahydro- → 1-(Ethylsulfonyl)-4-[(tetrahydro-2-furanyl)methyl]-4-piperidinecarbonitrile

Participants

Reaction Steps

In a dry round bottom flask was placed 1-(ethylsulfonyl)-4-ethynylpiperidine (14) (6.7 g, 33.1 mmol) and anhydrous toluene (200 ml). To this was added 2-(bromomethyl)tetrahydrofuran (6.51 ml, 49.7 mmol). Solid KHMDS1.2 equiv (7.93 g, 39.7 mmol) was added in one portion at room temperature and an exotherm was observed. The solution was allowed to stir for 12 hours at which time it was quenched with saturated aq. NH4Cl solution (100 ml). To the mixture was added EtOAc (50 ml) and the solution was then extracted by dilution with 250 ml, water and 3 washes with EtOAc (75 ml each). The organic layer was washed with brine (200 ml) and dried over MgSO4. The organic solvent was removed in vacuo to give a yellow solid. The residue was purified by column chromatography on silica gel, eluting with EtOAc/Hexanes to give 1-(ethylsulfonyl)-4-(tetrahydrofuran-2-ylmethyl)piperidine-4-carbonitrile (15) as a off-white solid. MS 287 (M+1)

Provenance & Evidence