반응 #331675

반응 방정식

Boc2O

3-methylene-cyclobutane carboxylic acid

NaN3

→

N-Boc-3-methylene-cyclobutanamine

수율 34.9%

용매

THF

반응 조건

후처리

1. 1
   온도was heated at 45° C. overnight
2. 2
   온도The reaction was then cooled to 0° C.
3. 3
   기타was quenched with 10% aq. NaNO2 (180 mL)
4. 4
   기타The THF was evaporated
5. 5
   추출the aqueous layer was extracted with EtOAc (180 mL)
6. 6
   세척The organic layer was washed with 5% aq. NaHCO3 (2×20 mL), brine (30 ml)
7. 7
   건조dried over Na2SO4
8. 8
   여과filtered
9. 9
   농축concentrated to dryness
10. 10
    기타to yield a crude, which
11. 11
    기타was purified by flash chromatography (silica gel/hexanes:ethyl acetate: 0-90%)

실험 절차

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).

출처