Ethyl chloroformate → HCID 86736762, compound

2-(3-Amino-2-oxo-1-azetidinyl)-2-(2-thienyl)acetic acid (380 mg.) was suspended in dichloromethane (15 ml.), and to the suspension, there were added bis(trimethylsilyl) acetamide (0.60 g.) and N,N-dimethylformamide (0.25 ml.). The mixture was stirred at ambient temperature for 6 hours and insoluble materials were filtered off from the mixture, and to the filtrate, there was added bis(trimethylsilyl) acetamide (0.20 g.), whereafter the mixture was stirred for half an hour to prepare a dichloromethane solution. In the other hand, 4-(3-tert-butoxycarbonylamino-3-methoxycarbonylpropoxy)phenylglyoxylic acid (0.440 g.) was suspended in dichoromethane (10 ml.), and to the suspension, there were added triethylamine (0,.120 g.) and N,N-dimethylbenzylamine (two drops). The mixture was stirred for a while to dissolve it, and a dichloromethane solution (5 ml.) containing ethyl chloroformate (0.125 g.) was added dropwise to the solution at 31 60° C. in the course of 3 minutes, whereafter the mixture was stirred at the same temperature for 5 minutes and then at - 20° to -15° C. for 20 minutes to dissolve it. To this solution, there was dropwise added the dichloromethane solution, prepared above, at -60° C. in the course of 20 minutes, whereafter the mixture was stirred at the same temperature for half an h our, and then at 31 15° C. for half an hour. The stirring was continued at 0° C. for an hour and at 20° to 25° C. for additional 1.5 hours. The reaction mixture was evaporated to dryness under reduced pressure to give a residue, which was dissolved in an aqueous sodium bicarbonate. The resultant aqueous solution was washed with diethyl ether, adjusted to pH 5.5 with dilute hydrochloric acid and then washed with ethyl acetate. The aqueous solution was adjusted to pH 5.5 with dilute hydrochloric acid and extracted with ethyl acetate. The extract was evaporated to dryness under reduced pressure to give 2-[3-{4-(3-tert-butoxycarbonylamino-3-methoxycarbonylpropoxy)phenylglyoxyloylamino}-2-oxo-1-azetidinyl]-2-(2-thienyl)acetic acid (0/100 g.).

1. filtrationinsoluble materials were filtered off from the mixture
2. additionto the filtrate, there was added bis(trimethylsilyl) acetamide (0.20 g.)
3. stirringwhereafter the mixture was stirred for half an hour
4. customto prepare a dichloromethane solution
5. stirringThe mixture was stirred for a while
6. dissolutionto dissolve it
7. additionwas added dropwise to the solution at 31 60° C. in the course of 3 minutes, whereafter the mixture
8. stirringwas stirred at the same temperature for 5 minutes
9. dissolutionat - 20° to -15° C. for 20 minutes to dissolve it
10. customprepared above, at -60° C. in the course of 20 minutes
11. stirringwhereafter the mixture was stirred at the same temperature for half an h our
12. waitat 31 15° C. for half an hour
13. waitThe stirring was continued at 0° C. for an hour and at 20° to 25° C. for additional 1.5 hours
14. customThe reaction mixture was evaporated to dryness under reduced pressure
15. customto give a residue, which
16. washThe resultant aqueous solution was washed with diethyl ether
17. washwashed with ethyl acetate
18. extractionextracted with ethyl acetate
19. customThe extract was evaporated to dryness under reduced pressure

ORD record

ord-13169ecb477840cca5b4a0a9156e0678

Source dataset

uspto-grants-1984_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04472309