Water → HCID 67054912, compound

Temperature

0 °C

To a solution of propylene oxide (4.0 mL, 57 mmol) in DCM (160 mL) was added 2.0 M of trimethylaluminum in toluene (27 mL, 54 mmol) at −78° C. under N2. After being stirred at that temperature for 10 min, a solution of benzyl piperazine-1-carboxylate (from Aldrich, 9 mL, 40 mmol) in DCM (60 mL) was added. The resulting reaction mixture was stirred at −78° C. for 30 min. The reaction was then allowed to warm up to 0° C., stirring for another 30 min. To the reaction mixture was added sodium fluoride (8.2 g, 200 mmol) in one portion, followed by water (5.2 mL, 290 mmol) slowly and periodically at 0° C. The resulting suspension was rapidly stirred for 1 h at 0° C. and filtered through a short column of Celite and the column was subsequently washed with DCM (120 mL). The combined filtrates were dried over Na2SO4, concentrated and purified on silica gel (eluting with 0-10% MeOH in DCM) to provide the desired product (9.6 g, 76%). LCMS calculated for C15H23N2O3(M+H)+: m/z=279.2; Found: 279.3. 1H NMR (500 MHz, DMSO-d6): δ 7.39˜7.31 (5H, m), 8.07 (2H, s), 4.29 (1H, J=4.0 Hz), 3.75 (1H, m), 3.38 (4H, br s), 2.38 (4H, m), 2.24 (1H, dd, J=12.5 and 7.0 Hz), 2.17 (1H, dd, J=12.5 and 7.0 Hz), 1.04 (3H, d, J=6.0 Hz) ppm.

1. customThe resulting reaction mixture
2. stirringwas stirred at −78° C. for 30 min
3. stirringstirring for another 30 min
4. customperiodically at 0° C
5. stirringThe resulting suspension was rapidly stirred for 1 h at 0° C.
6. filtrationfiltered through a short column of Celite
7. washthe column was subsequently washed with DCM (120 mL)
8. dry with materialThe combined filtrates were dried over Na2SO4
9. concentrationconcentrated
10. custompurified on silica gel (eluting with 0-10% MeOH in DCM)

ORD record

ord-bbac926f00b547fca27b95785a7d90d0

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249145B2