2-amino-3-methylpentanoic acid--合成(NaNO2&HCl)-->2-chloro-3-methylpentanoic acid...
- YyLv 71 decade agoFavorite Answer
Organic Syntheses, Coll. Vol. 8, p.119 (1993); Vol. 66, p.151 (1988).
In a 4-L, three-necked, round-bottomed flask equipped with a mechanical stirrer, a 500-mL dropping funnel, and a two-necked adapter fitted with a thermometer and a reflux condenser, 1 mol of 2-amino-3-methylpentanoic acid is dissolved in 1300 mL of 5 N hydrochloric acid. The mixture is cooled to 0°C in an ice/sodium chloride bath and a precooled solution of 110 g (1.6 mol) of sodium nitrite in 400 mL of water is added dropwise at a rate of about 2 mL/min under vigorous stirring and efficient cooling so that the temperature of the reaction mixture is kept below 5°C. After 5 hr, the bath is removed and the reaction is allowed to stand overnight at room temperature. The reflux condenser is connected with a water aspirator and the flask is carefully evacuated with stirring for 3 hr to remove nitrogen oxides, whereupon the color changes from yellowish brown to pale yellow. While the mixture is stirred vigorously, 100 g of solid sodium carbonate is added carefully in small portions so as to prevent excessive foaming. The reaction mixture is extracted with four portions of 400 mL of diethyl ether. The combined ether layers are concentrated to ca. 300 mL using a rotary evaporator at atmospheric pressure. The solution is washed with 50 mL of saturated brine, which thereafter is reextracted with three portions of 100 mL of diethyl ether. The combined ethereal solutions are dried for 10 hr over calcium chloride. The ether is distilled off with a rotary evaporator at atmospheric pressure (bath temperature 40–50°C). The oily residue is transferred into a distillation flask (rinsing the remainder with small portions of ether) and then fractionally distilled at reduced pressure.