Sodium hydride → {4-[4-(1-Isopropylpiperidin-4-yloxy)phenyl]tetrahydropyran-4-ylmethyl}dimethyl-amine

Temperature

75 °C

4-(4-Dimethylaminomethyl-tetrahydro-pyran-4-yl)-phenol (532 mg, 2.26 mmol) in DMF (2 ml) was added to a solution of NaH (100 mg, 2.5 mmol) in DMF (2 ml) at room temperature under N2. The reaction was stirred for 1 hr and a solution of methanesulfonic acid 1-isopropyl-piperidin-4-yl ester (400 mg, 1.81 mmol) in DMF (1.3 ml) was slowly added. The reaction was heated to 75° C. and stirred for 6 hrs. The reaction was allowed to cool to room temperature and diluted with TBME (20 ml), water (10 ml) and 5M NaOH solution (10 ml). The organic layer was washed with 2.5M NaOH (2×20 ml), brine (2×20 ml), dried over MgSO4, filtered and concentrated in vacuo. The crude reaction was purified by column chromatography, eluting with DCM:MeOH:NH3 (98:1:1) to give the title compound as a white crystalline solid (113 mg, 17%). 1H NMR (400 MHz, CDCl3) δ7.20 (d, 2H), 6.87 (d, 2H), 4.27 (m, 1H), 3.75 (dt, 2H), 3.55 (td, 2H), 2.85-2.68 (m, 3H), 2.45-2.32 (m, 2H), 2.40 (s, 2H), 2.14-1.94 (m, 4H), 1.96 (s, 6H), 1.93-1.75 (m, 4H), 1.06 (d, 6H).

1. stirringstirred for 6 hrs
2. temperatureto cool to room temperature
3. washThe organic layer was washed with 2.5M NaOH (2×20 ml), brine (2×20 ml)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe crude reaction
8. customwas purified by column chromatography
9. washeluting with DCM:MeOH:NH3 (98:1:1)

ORD record

ord-6fc875d665734654ad23fb7467098cd4

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456164B2