反応 #155402

反応方程式

Boc2O

3-methylene-cyclobutane carboxylic acid

NaN3

→

N-Boc-3-methylene-cyclobutanamine

収率 34.9%

溶媒

THF

反応条件

後処理

1. 1
   温度was heated at 45° C. overnight
2. 2
   温度The reaction was then cooled to 0° C.
3. 3
   その他was quenched with 10% aq. NaNO2 (180 mL)
4. 4
   その他The THF was evaporated
5. 5
   抽出the aqueous layer was extracted with EtOAc (180 mL)
6. 6
   洗浄The organic layer was washed with 5% aq. NaHCO3 (2×20 mL), brine (30 ml)
7. 7
   乾燥dried over Na2SO4
8. 8
   ろ過filtered
9. 9
   濃縮concentrated to dryness
10. 10
    その他to yield a crude, which
11. 11
    その他was purified by flash chromatography (silica gel/hexanes:ethyl acetate: 0-90%)

実験手順

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).

出典