3-Methylenecyclobutanecarboxylic acid → tert-butyl N-(3-methylidenecyclobutyl)carbamate

Temperatur

40 °C

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, 2H), 4.79 (bs, 1H), 4.05-4.23 (m, 1H), 2.92-3.11 (m, 2H), 2.50-2.65 (m, 2H), 1.44 (s, 9H).

1. temperaturewas heated at 45° C. overnight
2. temperatureThe reaction was then cooled to 0° C.
3. customwas quenched with 10% aq. NaNO2 (180 mL)
4. customThe THF was evaporated
5. extractionthe aqueous layer was extracted with EtOAc (180 mL)
6. washThe organic layer was washed with 5% aq. NaHCO3 (2×20 mL), brine (30 ml)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated to dryness
10. customto yield a crude, which
11. customwas purified by flash chromatography (silica gel/hexanes:ethyl acetate: 0-90%)

ORD-Eintrag

ord-9db0a791dd5b485ca6e542a83e3f327a

Quelldatensatz

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08367625B2