Reaktion #555203

Reaktionsgleichung

1-bromo-4-chlorobutane

BuLi

iPr2NH

NH4Cl

ethyl 1-cyclobutanecarboxylate

→

ethyl 1-(4-chlorobutyl)-1-cyclobutanecarboxylate

Ausbeute 86.0%

Lösungsmittel

THF

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooled to −60° C.
2. 2
   Temperaturto warm to 0° C. in 20 min.
3. 3
   Temperaturcooled again to −60° C.
4. 4
   Temperaturafter which the temperature was raised to −20° C. in 15 min
5. 5
   workup.WAITAfter 1.5 h
6. 6
   Temperaturthe temperature was raised to −10° C.
7. 7
   workup.STIRRINGstirring
8. 8
   workup.WAITwas continued for 1 h
9. 9
   Sonstigeto reach rt
10. 10
    Extraktionextracted with Et2O (500 mL)
11. 11
    WaschenThe organic layer was washed with brine (250 mL)
12. 12
    Trocknendried (Na2SO4)
13. 13
    Sonstigeevaporated in vacuo
14. 14
    workup.DISTILLATIONThe remaining oil was purified by fractional distillation under reduced pressure

Vorschrift

Under an N2 atmosphere at ˜7° C., BuLi (2.5M in hexanes, 52.8 mL, 132 mmol) was added drop wise to a solution of iPr2NH (18.52 mL, 132 mmol, distilled from NaOH) in dry THF (70 mL) in 10 min. The reaction mixture was allowed to warm to rt, stirred for 0.5 h, cooled to −60° C. and then, ethyl 1-cyclobutanecarboxylate (prepared according to Török, B.; Molnár, Á., J. Chem. Soc. Perkin Trans. 1, 1993, 7, 801-804, 14.05 g, 110 mmol) in dry THF (30 mL) was added dropwise in 20 min. The resulting mixture was allowed to warm to 0° C. in 20 min., cooled again to −60° C. and then, a solution of 1-bromo-4-chlorobutane (19.1 mL, 165 mmol) in dry THF (30 mL) was added dropwise in 20 min, after which the temperature was raised to −20° C. in 15 min. After 1.5 h, the temperature was raised to −10° C. and stirring was continued for 1 h. The reaction mixture was allowed to reach rt, poured into a mixture of aqueous saturated NH4Cl (200 mL) and ice (50 mL) and extracted with Et2O (500 mL). The organic layer was washed with brine (250 mL), dried (Na2SO4) and evaporated in vacuo. The remaining oil was purified by fractional distillation under reduced pressure to give ethyl 1-(4-chlorobutyl)-1-cyclobutanecarboxylate (20.53 g, 86%) as a thin, colorless oil. 1H NMR (CDCl3): δ=4.13 (q, J=7.1 Hz, 2H), 3.51 (t, J=6.8 Hz, 2H), 2.50-2.32 (m, 2H), 1.96-1.70 (m, 8H), 1.40-1.20 (m, 2H), 1.26 (t, J=7.2 Hz, 3H). 13C NMR (CDCl3): δ=176.6, 60.3, 47.6, 44.8, 37.3, 32.8, 30.1 (2×), 22.4, 15.8, 14.4. HRMS calcd for C11H20(37Cl)O2 (MH+): 221.1122. found: 221.1116.

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