反应详情

温度

40 °C

Under nitrogen a solution (500 ml) of 2 M butyllithium in hexane is added to a stirred solution of 143.1 ml of diisopropylamine in 1.5 liters of tetrahydrofuran at -78° C. after which 261 g (0.81 mole) of ornithine dibenzaldimine methyl ester in 1.5 liters of tetrahydrofuran is added. Upon completion of the addition the reaction temperature is raised to 40° C. and maintained between 40° and 50° C. for 3 hours during which time chlorodifluoromethane gas is bubbled through the mixture with stirring. The reaction mixture is then treated with a saturated solution of sodium chloride. The organic material is extracted with ether, and the ether extract washed several times with sodium chloride solution, dried over magnesium sulfate and evaporated to give a viscous oil. The oil is stirred with 1 N HCl (1.5 1) for 3 hours, the mixture extracted several times with chloroform and the aqueous solution evaporated to dryness. The oily residue is refluxed with 12 N hydrochloric acid (1.5 1 ) for 16 hours, the cooled solution clarified by chloroform extraction before concentration, decolorization (charcoal), and further concentration to about 750 ml. The pH of the solution is adjusted to 3.5 by the addition of triethylamine, the solution treated again with charcoal before concentration to about 500 ml and dilution with 7-8 liters of acetone. The precipitated product is filtered off and washed with ethanol. The crude product is recrystallized by dissolving in about 150 ml hot water and treatment of the solution with hot ethanol (450 ml). On cooling crystals of 2-difluoromethyl-2,5-diaminopentanoic acid hydrochloride monohydrate separate 71 g (37%), m.p. 183° C.

1. additionis added
2. additionUpon completion of the addition the reaction temperature
3. customis bubbled through the mixture
4. additionThe reaction mixture is then treated with a saturated solution of sodium chloride
5. extractionThe organic material is extracted with ether
6. extractionthe ether extract
7. washwashed several times with sodium chloride solution
8. dry with materialdried over magnesium sulfate
9. customevaporated
10. customto give a viscous oil
11. extractionthe mixture extracted several times with chloroform
12. customthe aqueous solution evaporated to dryness
13. temperatureThe oily residue is refluxed with 12 N hydrochloric acid (1.5 1 ) for 16 hours
14. extractionthe cooled solution clarified by chloroform extraction before concentration, decolorization (charcoal), and further concentration to about 750 ml
15. additionThe pH of the solution is adjusted to 3.5 by the addition of triethylamine
16. additionthe solution treated again with charcoal before concentration to about 500 ml and dilution with 7-8 liters of acetone
17. filtrationThe precipitated product is filtered off
18. washwashed with ethanol
19. customThe crude product is recrystallized
20. dissolutionby dissolving in about 150 ml hot water
21. temperatureOn cooling crystals of 2-difluoromethyl-2,5-diaminopentanoic acid hydrochloride monohydrate
22. customseparate 71 g (37%), m.p. 183° C.