Water → {4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methanol

Participants

Reaction Conditions

Reaction Steps

Anhydrous tetrahydrofuran (141 ml, 10 vol) was charged rapidly onto stirred and cooled (0-5° C.) lithium aluminium hydride (6.2 g, 0.1634 mol, 0.44 wt) under nitrogen (Note: very exothermic). The resulting slurry was cooled to 0-5° C. and then a solution of methyl 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carboxylate (14.1 g, 0.04058 mol) in tetrahydrofuran (99 ml, 7 vol) was added dropwise over 30 minutes maintaining 0-5° C. On complete addition the reaction was allowed to warm to room temperature over 30 minutes and stirred at 18-25° C. for 30 minutes, LC analysis showed the reaction to be complete. The mixture was cooled to 0 to 5° C., a 1:1 mixture of tetrahydrofuran and water (18.6 ml, 1.32 vol) was added very slowly (Note: very exothermic, gas evolution, temperature maintained below 16° C., toward the end of the quench the reaction mixture sets and then becomes freer with continued stirring.). The mixture was further quenched with 20% w/v sodium hydroxide solution (6.2 ml, 0.44 vol) and water (18.6 ml, 1.32 vol) and the resulting white suspension stirred vigorously for 30 minutes at 18-25° C. The slats were removed by filtration and rinsed with tetrahydrofuran (3×150 ml). The combined filtrates were evaporated to dryness at 40° C. to yield title compound (12.1 g, 94%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.25 (d, 2H), 6.90 (d, 2H), 4.05 (t, 2H), 3.80 (dt, 2H), 3.55 (td, 2H), 2.60 (t, 2H), 2.62-2.41 (m, 4H), 2.10 (dt, 2H), 2.00 (p, 2H), 2.00-1.85 (m, 2H), 1.95-1.72 (m, 4H).

Provenance & Evidence