Hydrochloric Acid → Ethyl 2-amino-1-methyl-1H-imidazole-5-carboxylate

Ethyl formate (500 mL) was added to sarcosin methyl ester hydrochloride (82 g, 585.7 mmol, grounded into powder prior to reaction) contained in a 1-L round-bottomed flask. The reaction mixture was cooled in an ice-water bath, stirred, a gas outlet connected with the flask, NaH (60% oil suspension, 54 g, 1.35 mol) added slowly during a period of 2 h, and stirred at rt for about 14 h. Volatiles were removed using a rotary evaporator to yield a residue which was triturated twice with hexane (500 mL) to yield a sticky light brown paste which was dissolved in ethanol (400 mL) and conc. HCl (50 mL) and stirred at 110° C. for 1.5 h. After the reaction mixture cooled, the white precipitate was filtered off and the residue washed with 2×25 mL of ethanol. The filtrate was evaporated to yield a thick brown oil to which was added 10% aqueous HOAc, H2NCN (45 g, 1.07 mol), and sodium acetate (88 g, 1.07 mol). The reaction mixture was stirred at 90-100° C. for 1.5 h to yield a clear solution which was cooled, its pH adjusted to 1 using concentrated HCl and the resulting solution concentrated to ⅕ its original volume using a rotary evaporator at a temperature not more than 45° C. The concentrated reaction mixture was carefully neutralized by addition of K2CO3 to a pH of 8-9 and extracted with EA (5×200 mL followed by 3×50 mL). The combined ethyl acetate layers were dried over MgSO4, filtered, and volatiles removed to yield 48 g of 1-N-methyl-2-amino imidazole-5-carboxylic acid ethyl ester.

1. customto reaction)
2. customcontained in a 1-L round-bottomed flask
3. temperatureThe reaction mixture was cooled in an ice-water bath
4. additionadded slowly during a period of 2 h
5. stirringstirred at rt for about 14 h
6. customVolatiles were removed
7. customa rotary evaporator
8. customto yield a residue which
9. customwas triturated twice with hexane (500 mL)
10. customto yield a sticky light brown paste which
11. temperatureAfter the reaction mixture cooled
12. filtrationthe white precipitate was filtered off
13. washthe residue washed with 2×25 mL of ethanol
14. customThe filtrate was evaporated
15. customto yield a thick brown oil to which
16. stirringThe reaction mixture was stirred at 90-100° C. for 1.5 h
17. customto yield a clear solution which
18. temperaturewas cooled
19. concentrationthe resulting solution concentrated
20. customa rotary evaporator at a temperature not more than 45° C
21. customThe concentrated reaction mixture
22. extractionextracted with EA (5×200 mL followed by 3×50 mL)
23. dry with materialThe combined ethyl acetate layers were dried over MgSO4
24. filtrationfiltered
25. customvolatiles removed

ORD record

ord-8257768f9b0f4c8c8dd0e9ce87b16e1a

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08003625B2