Hydrochloric Acid → HCID 56981020, compound

To a suspension of sodium borohydride (1.87 g) in tetrahydrofuran (75 ml) was added boron trifluoride etherate (18.7 ml) in a nitrogen stream with stirring at 0°-10° C. The mixture was stirred at the same temperature for 30 minutes. To the mixture was added a solution of (2S,4R)-4-methanesulfonyloxy-2-(methylcarbamoyl)methyloxymethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (7.35 g) in tetrahydrofuran (7.5 ml) at 0°-10° C. The mixture was stirred at the same temperature for 3 hours and at ambient temperature overnight. Methanol (5 ml) was added to the reaction mixture at 0°-10° C. After 2 hours, insoluble material was filtered off and the filtrate was concentrated under reduced pressure to give a residue. A solution of the residue in a mixture of concentrated hydrochloric acid (7 ml) and methanol (70 ml) was stirred at ambient temperature overnight. The mixture was concentrated under reduced pressure to give a syrup. The syrup was dissolved in ethyl acetate (75 ml), washed with water (75 ml×2) and brine (75 ml) in turn, dried over magnesium sulfate, and concentrated under reduced pressure to give a syrup. The syrup was dissolved in a mixture of water (30 ml) and tetrahydrofuran (30 ml), and to this mixture was added a solution of 4-nitrobenzyloxycarbonyl chloride (3.55 g) in tetrahydrofuran (7 ml) under ice-cooling with stirring, keeping the pH between 8.5-9.5 with 4N aqueous sodium hydroxide. The mixture was stirred at the same condition for 2 hours. The tetrahydrofuran was removed under reduced pressure from the reaction mixture and ethyl acetate (50 ml) was added thereto. The organic layer was separated, dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (100 g) and eluted with a mixture of methanol and chloroform (1:99 V/V) to give (2S,4R)-4-methanesulfonyloxy-2-[2-{N-methyl-N-(4-nitrobenzyloxycarbonyl)amino}ethyloxymethyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (8.33 g).

1. stirringThe mixture was stirred at the same temperature for 30 minutes
2. stirringThe mixture was stirred at the same temperature for 3 hours and at ambient temperature overnight
3. filtrationinsoluble material was filtered off
4. concentrationthe filtrate was concentrated under reduced pressure
5. customto give a residue
6. stirringwas stirred at ambient temperature overnight
7. concentrationThe mixture was concentrated under reduced pressure
8. customto give a syrup
9. washwashed with water (75 ml×2) and brine (75 ml) in turn
10. dry with materialdried over magnesium sulfate
11. concentrationconcentrated under reduced pressure
12. customto give a syrup
13. temperaturecooling
14. stirringwith stirring
15. stirringThe mixture was stirred at the same condition for 2 hours
16. customThe tetrahydrofuran was removed under reduced pressure from the reaction mixture and ethyl acetate (50 ml)
17. additionwas added
18. customThe organic layer was separated
19. dry with materialdried over magnesium sulfate
20. concentrationconcentrated under reduced pressure
21. customto give a syrup
22. washeluted with a mixture of methanol and chloroform (1:99 V/V)

ORD record

ord-89450c377a31495e9974a960b6507dec

Source dataset

uspto-grants-1991_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04983596