Reaktion #66334

Reaktionsgleichung

Boc2O

3-methylene-cyclobutane carboxylic acid

NaN3

→

N-Boc-3-methylene-cyclobutanamine

Ausbeute 34.9%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas heated at 45° C. overnight
2. 2
   TemperaturThe reaction was then cooled to 0° C.
3. 3
   Sonstigewas quenched with 10% aq. NaNO2 (180 mL)
4. 4
   SonstigeThe THF was evaporated
5. 5
   Extraktionthe aqueous layer was extracted with EtOAc (180 mL)
6. 6
   WaschenThe organic layer was washed with 5% aq. NaHCO3 (2×20 mL), brine (30 ml)
7. 7
   Trocknendried over Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated to dryness
10. 10
    Sonstigeto yield a crude, which
11. 11
    Sonstigewas purified by flash chromatography (silica gel/hexanes:ethyl acetate: 0-90%)

Vorschrift

To a stirring solution of 3-methylene-cyclobutane carboxylic acid (1.0 g, 8.9 mmol) in THF (90 mL) was added NaN3 (2.0 g, 31.1 mmol), followed by tetrabutyl ammonium bromide (0.48 g, 1.5 mmol) and Zn(OTf)2 (0.1 g, 0.3 mmol), and the reaction mixture was heated to 40° C. Boc2O (2.1 g, 9.8 mmol) was then added at once, and the reaction was heated at 45° C. overnight. The reaction was then cooled to 0° C. and was quenched with 10% aq. NaNO2 (180 mL). The THF was evaporated and the aqueous layer was extracted with EtOAc (180 mL). The organic layer was washed with 5% aq. NaHCO3 (2×20 mL), brine (30 ml), dried over Na2SO4, filtered and concentrated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate: 0-90%) to yield the desired N-Boc-3-methylene-cyclobutanamine (0.57 g, 3.1 mmol, 34.9% yield): 1H NMR (250 MHz, CDCl3) δ 4.83 (s, 2 H), 4.79 (bs, 1 H), 4.05-4.23 (m, 1 H), 2.92-3.11 (m, 2 H), 2.50-2.65 (m, 2 H), 1.44 (s, 9 H).

Quelle