Carbon Dioxide → HCID 21312941, compound

Temperature

35 °C

Under anhydrous conditions, a solution of approximately 1.2 mol of n-butyl lithium in n-hexane was added dropwise over 3 hours to an efficiently cooled solution of 66 g (0.58 mol) of 3-hydroxymethyl-5-methyl-1,2,4-oxadiazol and 87 ml of N,N,N',N'-tetramethyl ethylene diamine in 1200 ml of tetrahydrofuran and during the addition, the reaction temperature was not allowed to rise above -70° C. The reaction mixture was stirred for 1 hour at -70° C. and under efficient cooling, dried gaseous carbon dioxide was passed over the surface of the stirred reaction mixture for ten hours at -70° C. Subsequently, the temperature was allowed to rise gradually to -5° C. and the formed precipitate was collected by vacuum filtration and was washed with dry ethyl acetate and with n-hexane. The precipitate was dissolved slowly by adding it in small portions to a stirred icy-cold mixture of 500 ml of water and 500 ml of diethyl ether and concentrated phosphoric acid was added till the pH was 4.0. The layers were separated and the organic layer discarded. The water-layer was further acidified to a pH of 2.0 and subsequently evaporated in vacuo. Remnants of water in the residue were removed in vacuo with the help of benzene and the residue was dried in vacuo over phosphorous pentoxide for 16 hours. The syrupy product was stirred with 500 ml of acetone at about 35° C. and the acetone was decanted. This was repeated once whereupon the residue became a solid mass which was transferred to a filter and repeatedly stirred with 500 ml portions of acetone until according to thin-layer chromatograms the filtrate no longer contained the desired compound. All filtrates were combined (total of about 4000 ml) and concentrated in vacuo to a volume of about 300 ml. 600 ml of ethyl acetate were added and the resulting solution was again concentrated in vacuo to a final volume of about 250 ml. The resulting crystalline precipitate was vacuum filtered, washed with dry ethyl acetate and with carbon tetrachloride. After drying in vacuo, 41 g of 3-hydroxymethyl-1,2,4-oxadiazol-5-yl-acetic acid were obtained with melting and decomposition taking place between about 96° and 98° C. The filtrate was evaporated in vacuo and the oily residue was repeatedly stirred with small volumes of dichloromethane. The resulting solid was transferred to a filter and washed with ethyl acetate and carbon tetrachloride. After drying, the second crop of said product weighed 14.1 g and melted with extensive decomposition at 92°-96° C. According to thin-layer chromatograms, IR and PMR spectra both crops were virtually identical for a total of 45.1 g (about 55% yield) of about 96% purity.

1. customto rise above -70° C
2. customwas passed over the surface of the stirred reaction mixture for ten hours at -70° C
3. customto rise gradually to -5° C.
4. filtrationthe formed precipitate was collected by vacuum filtration
5. washwas washed with dry ethyl acetate and with n-hexane
6. dissolutionThe precipitate was dissolved slowly
7. additionby adding it in small portions
8. additionto a stirred icy-cold mixture of 500 ml of water and 500 ml of diethyl ether and concentrated phosphoric acid
9. additionwas added till the pH was 4.0
10. customThe layers were separated
11. customsubsequently evaporated in vacuo
12. customRemnants of water in the residue were removed in vacuo with the help of benzene
13. dry with materialthe residue was dried in vacuo over phosphorous pentoxide for 16 hours
14. customthe acetone was decanted
15. filtrationa filter
16. stirringrepeatedly stirred with 500 ml portions of acetone
17. concentrationconcentrated in vacuo to a volume of about 300 ml
18. addition600 ml of ethyl acetate were added
19. concentrationthe resulting solution was again concentrated in vacuo to a final volume of about 250 ml
20. filtrationfiltered
21. washwashed with dry ethyl acetate and with carbon tetrachloride
22. customAfter drying in vacuo

ORD record

ord-e40b68c04d804e629af819087dfc7eac

Source dataset

uspto-grants-1979_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04160829