Реакция #1121723

Уравнение реакции

4-methyl piperazine

tert-butyl 3-bromopropionate

→

tert-butyl 3-(4-methylpiperazin-1-yl)propanoate

Выход 99.8%

Растворители

—

Hexanes

ethyl acetate

EtOAc

methylene chloride

Условия реакции

Обработка

1. 1
   Температураheated on an oil bath to 55° C. for 2 h
2. 2
   Другоеconsumption of the bromide reagent
3. 3
   workup.ADDITIONThe reaction was diluted with EtOAc (100 mL)
4. 4
   Другоеtransferred to a separatory funnel
5. 5
   Промывкаthe organic phase was washed with water (100 mL), NaHCO3 (sat'd, 2×100 mL), and brine (100 mL)
6. 6
   Сушкаdried over MgSO4
7. 7
   Концентрированиеconcentrated
8. 8
   Другоеto give a slightly yellow oil
9. 9
   Промывкаthe desired product was eluted from the silica
10. 10
    Температураwith increasingly polar
11. 11
    Температураeluent (EtOAc in hexanes, starting at 20%, 200 mL volumes increasing in 15% increments to 100%)
12. 12
    workup.ADDITIONFractions containing the desired material
13. 13
    Концентрированиеwere concentrated

Методика

4-methyl piperazine (7.68 mL, 70 mmol, 4 equiv) was added to a stirred solution of tert-butyl 3-bromopropionate (3.0 mL, 18 mmol) in ethyl acetate (15 mL) at 0° C. The solution was stirred at 25° C. for 1 h with evolution of a white precipitate, then heated on an oil bath to 55° C. for 2 h. TLC analysis (20% EtOAc in Hexanes, Rf=0.9 (starting material), 0.1 (product)) indicated complete consumption of the bromide reagent. The reaction was diluted with EtOAc (100 mL) and transferred to a separatory funnel, and the organic phase was washed with water (100 mL), NaHCO3 (sat'd, 2×100 mL), and brine (100 mL), dried over MgSO4 and concentrated to give a slightly yellow oil. The oil was dissolved in methylene chloride (20 mL), loaded on to a pre-equilibrated plug of silica gel (20% EtOAc in Hexanes, 150 mL SiO2) and the desired product was eluted from the silica with increasingly polar eluent (EtOAc in hexanes, starting at 20%, 200 mL volumes increasing in 15% increments to 100%). Fractions containing the desired material were concentrated to give tert-butyl 3-(4-methylpiperazin-1-yl)propanoate (4.1 g, quantitative). 1H NMR (400 MHz, CDCl3) δ (ppm)=3.45 (d, J=3 Hz, 2H), 2.64 (t, J=7.3 Hz, 2H), 2.47 (br s, 6H), 2.38 (t, J=7.3 Hz, 2H), 2.25 (s, 3H), 1.42 (s, 9H).

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