Hydrochloric Acid → HCID 131713002, compound

Temperature

-15 °C

3.46 g (15 mmoles) of BOC-Leu-OH are dissolved in 50 ml of ethyl acetate, 2.1 ml (15 mmoles) of triethylamine are added, and the mixture is cooled to -15° C. 1.97 ml (16 mmoles) of pivaloyl chloride are added dropwise to the stirred mixture at such a rate that the temperature remains below -10° C., the resulting suspension is stirred for 10 minutes, and then 1.37 ml (16.5 mmoles) of pyrrolidine are added dropwise to the suspension at the same temperature. When the addition is complete, the mixture is stirred at -10° C. for additional 30 minutes, and then allowed to stand at 5° C. for 3 hours. The reaction mixture is shaken thrice with 10 ml of n hydrochloric acid, each, thrice with 10 ml of n sodium hydrocarbonate solution, each, and then with 10 ml of water, dried over anhydrous sodium sulfate, and evaporated in vacuo. The oily residue is dissolved in 5 ml of ethyl acetate, and 10 ml of a 5 n hydrochloric acid solution in ethyl acetate are added. After one hour of standing the solution is diluted with ether and extracted with water. The aqueous solution is washed with ether, rendered alkaline with potassium carbonate, and then extracted with chloroform. The chloroform solution is dried over anhydrous sodium sulfate, evaporated, the oily residue is dissolved in 10 ml of ether, and the pH of the solution is adjusted to 3 with a concentrated solution of hydrochloric acid in ethyl acetate. The separated crystals are filtered off to obtain 2.41 g (73%) of H-Leu-pyrrolidine.HCl; m.p.: 170°-174° C. (decomposition), Rf5 =0.37.

1. customremains below -10° C.
2. additionWhen the addition
3. stirringthe mixture is stirred at -10° C. for additional 30 minutes
4. waitto stand at 5° C. for 3 hours
5. dry with materialeach, thrice with 10 ml of n sodium hydrocarbonate solution, each, and then with 10 ml of water, dried over anhydrous sodium sulfate
6. customevaporated in vacuo
7. dissolutionThe oily residue is dissolved in 5 ml of ethyl acetate
8. addition10 ml of a 5 n hydrochloric acid solution in ethyl acetate are added
9. waitAfter one hour of standing
10. additionthe solution is diluted with ether
11. extractionextracted with water
12. washThe aqueous solution is washed with ether
13. extractionextracted with chloroform
14. dry with materialThe chloroform solution is dried over anhydrous sodium sulfate
15. customevaporated
16. dissolutionthe oily residue is dissolved in 10 ml of ether
17. filtrationThe separated crystals are filtered off

ORD record

ord-5c76f19f235b4acb9bbf5e1e42217bf8

Source dataset

uspto-grants-1983_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04386073