Phosphorus pentachloride → HCID 22871520, compound

Temperature

-40 °C

To a solution of isomer (i) of N-(N-benzyloxycarbonyl-L-prolyl)-2-(2-cyanoethyl)alanine methyl ester (3.0 g) in dichloromethane (30 ml) was added 1.7 g of phosphorus pentachloride, and the resulting mixture was refluxed for 30 minutes. The solvent was distilled off under reduced pressure and the residue was dissolved in dichloromethane (40 ml). The solution was cooled to -40° C. in a cooling bath, and propanol (5 ml) and triethylamine (10 ml) were added. The cooling bath was removed and the mixture was stirred for 30 minutes, then for another 1.5 hours at room temperature. The solvent was distilled off under reduced pressure and the residue was dissolved in methanol (30 ml). The methanol solution was cooled to 5° C., 30 ml of 0.5 N hydrochloric acid were added, and the mixture was stirred for 1.5 hours at room temperature. Water (50 ml) was added and the mixture was then washed with diethyl ether (100 ml). The aqueous layer was adjusted to about pH 8 with sodium bicarbonate solution and extracted with dichloromethane (100 ml×3). The combined organic extracts were dried over magnesium sulphate and the solvent was distilled off. The residue was purified by silica gel column chromatography, eluted with ethyl acetate, to give 0.91 g of isomer (i) of the desired product as a pale yellow liquid.

1. temperaturethe resulting mixture was refluxed for 30 minutes
2. distillationThe solvent was distilled off under reduced pressure
3. dissolutionthe residue was dissolved in dichloromethane (40 ml)
4. additionpropanol (5 ml) and triethylamine (10 ml) were added
5. customThe cooling bath was removed
6. waitfor another 1.5 hours at room temperature
7. distillationThe solvent was distilled off under reduced pressure
8. dissolutionthe residue was dissolved in methanol (30 ml)
9. temperatureThe methanol solution was cooled to 5° C.
10. addition30 ml of 0.5 N hydrochloric acid were added
11. stirringthe mixture was stirred for 1.5 hours at room temperature
12. additionWater (50 ml) was added
13. washthe mixture was then washed with diethyl ether (100 ml)
14. extractionextracted with dichloromethane (100 ml×3)
15. dry with materialThe combined organic extracts were dried over magnesium sulphate
16. distillationthe solvent was distilled off
17. customThe residue was purified by silica gel column chromatography
18. washeluted with ethyl acetate

ORD record

ord-082dae2c9b9d48c8afa20f41b5214d79

Source dataset

uspto-grants-1985_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04545942