1,2-Dibromoethane → 1-Methyl-4-(5-vinylpyridin-2-yl)piperazine

Temperature

95 °C

A sealed, degassed mixture of powdered KOH (123 mg, 2.2 mmol) and 1,2-dibromoethane (0.05 mL, 0.6 mmol) in anh THF (2 mL) under Ar was heated under microwave irradiation at 95° C. for 70 min. The reaction mixture was then cooled to rt and treated with Pd(OAc)2 (5.0 mg, 0.022 mmol), PPh3 (11.5 mg, 0.044 mmol), 1-methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine (120 mg, 0.39 mmol) and degassed MeOH (2 mL). The sealed reaction mixture was heated again under microwave irradiation at 95° C. for 60 min. The crude mixture was concentrated under reduced pressure and purified by prepTLC (SiO2 10% MeOH/DCM) to provide the title compound a colorless gum (0.18 g, quantitative): 1H NMR (400 MHz, CD3OD) δ ppm 8.07 (d, J=2.26 Hz, 1H), 7.73 (dd, J=8.91, 2.38 Hz, 1H), 6.82 (d, J=9.03 Hz, 1H), 6.62 (dd, J=17.82, 11.04 Hz, 1H), 5.63 (d, 1H), 5.12 (d, J=10.79 Hz, 4 H), 3.52-3.66 (m, 4H), 2.50-2.61 (m, 4H), 2.35 (s, 3H); MS ESI 204.0 [M+H]+, calcd for [C12H17N3+H]+ 204.3.

1. customA sealed, degassed
2. temperatureThe reaction mixture was then cooled to rt
3. customdegassed MeOH (2 mL)
4. customThe sealed reaction mixture
5. temperaturewas heated again under microwave irradiation at 95° C. for 60 min
6. concentrationThe crude mixture was concentrated under reduced pressure
7. custompurified by prepTLC (SiO2 10% MeOH/DCM)

ORD record

ord-77a830e9dbe241e080860e81119dc325

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263596B2