Reacción #9878

Ecuación de reacción

HCl

benzylmalonic acid

paraformaldehyde

diethylamine

→

compound 17

Rendimiento 90.0%

2-methylene-3-phenylpropanoic acid

Rendimiento 90.0%

Disolventes

water

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe reaction temperature below 20° C. (see FIG. 6)
2. 2
   TemperaturaThe reaction was then warmed
3. 3
   Temperaturato reflux for 90 min
4. 4
   Temperaturacooled again on ice
5. 5
   Otrothe reaction temperature below 10° C
6. 6
   OtroThe phases were then separated
7. 7
   LavadoThe organic layer was washed with brine (100 mL)
8. 8
   Secadodried over sodium sulfate
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónthe filtrate concentrated under vacuum

Procedimiento

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%.

Fuente