Dichloromethane → 5-(2-piperazin-1-ylethyl)-2-benzofuran-1(3H)-one hydrochloride

Temperature

-78 °C

5-(prop-2-en-1-yl)-2-benzofuran-1(3H)-one (2.30 g, 13.2 mmol) was dissolved in DCM (30 mL) and cooled to −78° C. Ozone was bubbled through the solution until the color changed (to orange). Nitrogen was bubbled through the solution for about one minute to remove any residual ozone. tert-Butyl piperazine-1-carboxylate (1.64 g, 8.80 mmol) in DCM was added followed by sodium triacetoxyborohydride (11.2 g, 52.8 mmol). The reaction mixture was permitted to warm to room temperature and was stirred overnight. The reaction mixture was partitioned between DCM and water. The organic layer was washed with brine, then dried over MgSO4. The crude product was purified by preparative TLC eluting with 5% methanol in DCM. The resulting 1,1-dimethylethyl-4-[2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazine-1-carboxylate was deprotected (of Boc) as described in Method 1 of the synthesis of 5.

1. customOzone was bubbled through the solution until the color
2. customNitrogen was bubbled through the solution for about one minute
3. customto remove any residual ozone
4. temperatureto warm to room temperature
5. customThe reaction mixture was partitioned between DCM and water
6. washThe organic layer was washed with brine
7. dry with materialdried over MgSO4
8. customThe crude product was purified by preparative TLC
9. washeluting with 5% methanol in DCM
10. customas described in Method 1 of the synthesis of 5

ORD record

ord-3a56b56fd1744852bef5ea541df3ee3a

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056859B2