Реакция #155402

Уравнение реакции

Boc2O

3-methylene-cyclobutane carboxylic acid

NaN3

→

N-Boc-3-methylene-cyclobutanamine

Выход 34.9%

Растворители

THF

Условия реакции

Обработка

1. 1
   Температураwas heated at 45° C. overnight
2. 2
   ТемператураThe reaction was then cooled to 0° C.
3. 3
   Другоеwas quenched with 10% aq. NaNO2 (180 mL)
4. 4
   ДругоеThe THF was evaporated
5. 5
   Экстракцияthe aqueous layer was extracted with EtOAc (180 mL)
6. 6
   ПромывкаThe organic layer was washed with 5% aq. NaHCO3 (2×20 mL), brine (30 ml)
7. 7
   Сушкаdried over Na2SO4
8. 8
   Фильтрацияfiltered
9. 9
   Концентрированиеconcentrated to dryness
10. 10
    Другоеto yield a crude, which
11. 11
    Другоеwas purified by flash chromatography (silica gel/hexanes:ethyl acetate: 0-90%)

Методика

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).

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