Reaction #155402

Reaction equation

Boc2O

3-methylene-cyclobutane carboxylic acid

NaN3

→

N-Boc-3-methylene-cyclobutanamine

Yield 34.9%

Solvents

THF

Conditions

Workup

1. 1
   Temperaturewas heated at 45° C. overnight
2. 2
   TemperatureThe reaction was then cooled to 0° C.
3. 3
   Otherwas quenched with 10% aq. NaNO2 (180 mL)
4. 4
   OtherThe THF was evaporated
5. 5
   Extractionthe aqueous layer was extracted with EtOAc (180 mL)
6. 6
   WashThe organic layer was washed with 5% aq. NaHCO3 (2×20 mL), brine (30 ml)
7. 7
   Dryingdried over Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated to dryness
10. 10
    Otherto yield a crude, which
11. 11
    Otherwas purified by flash chromatography (silica gel/hexanes:ethyl acetate: 0-90%)

Procedure

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).

Source