Water → HCID 15730468, compound

Temperature

18 °C

Aluminium chloride (97 g, 731 mmol) was added over 30 seconds to stirred DCM (3 L) under argon at 16° C. resulting in a temp rise to 20° C. When this had dissolved (approx 5 mins) and the temp had cooled to 18° C., ethyl-2-propynate (71.7 g, 731 mmol) was added. A solution of 2-methylfuran (60 g, 731 mmol) in DCM (600 ml) was added to the stirred solution over 35 minutes resulting in a measured exotherm 20.5° C. The exotherm was controlled by a Huber cooling unit and the observed temp range during the addition was 18° C.-20.5° C. After the addition was complete the brown reaction mixture was stirred at 20° C. After a total of 50 mins at 20° C., the reaction mixture was poured into water (3 L) and ice (1 Kg) with stirring to give a yellow mixture. This was transferred to a separating funnel and shaken vigorously. The layers were separated and the aqueous phase further extracted with DCM (1 L). The combined organic extracts were re-washed with water (1.5 L), dried (Na2SO4) and filtered through Kieselguhr. The filtrate was concentrated in vacuo to a brown/green oil. This was purified by silica gel flash chromatography on 2 Biotage 75 L columns in toluene (700 ml) and the solution split into 2 equal portions and each passed through a 75 L column, collecting 400 ml fractions and eluting with the following solvent eluant systems:

1. customresulting in a temp rise to 20° C
2. dissolutionWhen this had dissolved (approx 5 mins)
3. customresulting in a measured exotherm 20.5° C
4. temperaturecooling unit
5. additionthe observed temp range during the addition
6. customwas 18° C.-20.5° C
7. additionAfter the addition
8. stirringwith stirring
9. customto give a yellow mixture
10. customThis was transferred to a separating funnel
11. stirringshaken vigorously
12. customThe layers were separated
13. extractionthe aqueous phase further extracted with DCM (1 L)
14. washThe combined organic extracts were re-washed with water (1.5 L)
15. dry with materialdried (Na2SO4)
16. filtrationfiltered through Kieselguhr
17. concentrationThe filtrate was concentrated in vacuo to a brown/green oil
18. customThis was purified by silica gel flash chromatography on 2 Biotage 75 L columns in toluene (700 ml)
19. customthe solution split into 2 equal portions
20. customcollecting 400 ml fractions
21. washeluting with the following solvent eluant systems

ORD record

ord-effedf2550d64d08a70523a944627ce1

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314147B2