Reaktion #555191

Reaktionsgleichung

H2O

NaH

TosMIC

tert-Butyl 1-(4-bromo-butyl)-cyclopropanecarboxylate

→

tert-butyl 1-{9-[1-(tert-butoxycarbonyl)cyclopropyl]-5-isocyano-5-[(4-methylphenyl)sulfonyl]nonyl}-1-cyclopropanecarboxylate

Lösungsmittel

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooling with a water bath
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITwas continued for 1 h and 50 min
4. 4
   Extraktionthe resulting mixture was extracted with Et2O (3×100 mL)
5. 5
   WaschenThe combined organic layers were washed with brine (2×100 mL)
6. 6
   Trocknendried (Na2SO4)
7. 7
   Sonstigeevaporated in vacuo
8. 8
   SonstigeThe remaining oil was purified by column chromatography (silica, heptane:EtOAc=6:1)

Vorschrift

Under a N2 atmosphere, NaH (60% (%) in mineral oil, 2.91 g, 72.8 mmol) was added portion wise to a solution of TosMIC (5.85 g, 30.0 mmol) and Bu4NI (1.10 g, 2.98 mmol) in dry DMSO (100 mL) while stirring vigorously and cooling with a water bath. After 10 min, tert-Butyl 1-(4-bromo-butyl)-cyclopropanecarboxylate (16.56 g, 94% pure by GC, 56.2 mmol) was added drop wise in 20 min and stirring was continued for 1 h and 50 min. Then, H2O (100 mL) was added drop wise and the resulting mixture was extracted with Et2O (3×100 mL). The combined organic layers were washed with brine (2×100 mL), dried (Na2SO4) and evaporated in vacuo. The remaining oil was purified by column chromatography (silica, heptane:EtOAc=6:1) to give tert-butyl 1-{9-[1-(tert-butoxycarbonyl)cyclopropyl]-5-isocyano-5-[(4-methylphenyl)sulfonyl]nonyl}-1-cyclopropanecarboxylate (10.00 g) as a slightly yellow oil. The above mentioned oil (10.00 g) was dissolved in CH2Cl2 (200 mL) and conc aqueous HCl (4 mL) was added. After stirring vigorously for 1 h, H2O (100 mL) was added and the layers were separated. The aqueous phase was extracted with CH2Cl2 (100 mL) and the combined organic layers were washed with saturated aqueous NaHCO3 (3×100 mL), dried (Na2SO4) and evaporated in vacuo. The remaining residue was purified by column chromatography (silica, heptane:EtOAc=10:1) to give tert-butyl 1-[9-[1-(tert-butoxycarbonyl)cyclopropyl]-5-oxononyl]-1-cyclopropanecarboxylate (5.80 g, 49%) as a colorless oil. 1H NMR (CDCl3): δ=2.39 (t, J=7.3 Hz, 4H), 1.63-1.38 (m, 30H), 1.10 (dd, J=6.6, 3.9 Hz, 4H), 0.59 (dd, J=6.7, 3.9 Hz, 4H). 13C NMR (CDCl3): δ=211.1, 174.4 (2×), 79.9 (2×), 42.7 (2×), 33.9 (2×), 28.0 (6×), 27.4 (2×), 24.1 (2×), 24.0 (2×), 15.2 (4×). HRMS calcd for C25H43O5 (MH+): 423.3111. found: 423.3111.

Quelle