Benzyl piperazine-1-carboxylate → Benzyl 4-(2-(benzyloxy)pyridin-3-yl)piperazine-1-carboxylate

Temperature

80 °C

To a stirred suspension of 0.011 g (0.012 mmol) of (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-palladium (3:2) in 3 mL of anhydrous toluene under an atmosphere of nitrogen was added 0.015 g (0.037 mmol) of 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine and the resulting mixture was allowed to stir for 20 min. Next, 0.11 g (0.41 mmol) of 2-(benzyloxy)-3-bromopyridine was added followed by 0.11 g (0.49 mmol) of benzyl piperazine-1-carboxylate and 0.059 g (0.61 mmol) of sodium tert-butoxide. The resulting mixture was then heated to 80° C. overnight. After cooling to ambient temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water then brine, dried over magnesium sulfate and evaporated to dryness in vacuo. The residue was purified by silica gel chromatography eluting with a 0-100% acetone in hexanes gradient to afford the title compound as clear gum (0.090 g, 55%). 1H-NMR (500 MHz, CDCl3) δ 7.84 (dd, J=4.9, 1.6 Hz, 1H), 7.47-7.29 (m, 10H), 7.09 (dd, J=7.5, 1.6 Hz, 1H), 6.87 (dd, J=7.5, 4.9 Hz, 1H), 5.46 (s, 2H), 5.16 (s, 2H), 3.67-3.65 (m, 4H), 3.07 (br s, 4H). LC-MS: m/z (ES) 404.0 (MH)+.

1. temperatureAfter cooling to ambient temperature
2. extractionextracted with ethyl acetate
3. washThe combined organic layers were washed with water
4. dry with materialbrine, dried over magnesium sulfate
5. customevaporated to dryness in vacuo
6. customThe residue was purified by silica gel chromatography
7. washeluting with a 0-100% acetone in hexanes gradient

ORD record

ord-c69d606ce85b4564ae29aa1d539c9d58

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354403B2