Реакция #9878

Уравнение реакции

HCl

benzylmalonic acid

paraformaldehyde

diethylamine

→

compound 17

Выход 90.0%

2-methylene-3-phenylpropanoic acid

Выход 90.0%

Растворители

water

ethyl acetate

Условия реакции

Обработка

1. 1
   Другоеthe reaction temperature below 20° C. (see FIG. 6)
2. 2
   ТемператураThe reaction was then warmed
3. 3
   Температураto reflux for 90 min
4. 4
   Температураcooled again on ice
5. 5
   Другоеthe reaction temperature below 10° C
6. 6
   ДругоеThe phases were then separated
7. 7
   ПромывкаThe organic layer was washed with brine (100 mL)
8. 8
   Сушкаdried over sodium sulfate
9. 9
   Фильтрацияfiltered
10. 10
    Концентрированиеthe filtrate concentrated under vacuum

Методика

A solution of benzylmalonic acid (20.0 g, 0.103 mol, 1 eq) and paraformaldehyde (4.94 g, 0.164 mol, 1.6 eq) in ethyl acetate (150 mL) was cooled (0° C.) and treated with diethylamine (10.65 mL, 0.103 mol, 1 eq) drop wise, keeping the reaction temperature below 20° C. (see FIG. 6). The reaction was then warmed to reflux for 90 min and cooled again on ice. The homogeneous solution was treated with water (20 mL) and concentrated aqueous HCl (12N) (9.0 mL, 0.108 mol) drop wise, keeping the reaction temperature below 10° C. The phases were then separated. The organic layer was washed with brine (100 mL), dried over sodium sulfate, filtered, and the filtrate concentrated under vacuum giving compound 17 as a white solid (15 g, 90%). Rf 0.46 (hexane/EtOAc=7:3). 1H NMR (300 MHz, CDCl3) δ 7.28 (m, 5H), 6.42 (s, 1H), 5.62 (s, 1H), 3.67 (s, 2H). [M−H]− 161.0: tR=2.53 min; purity: 99%.

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