Acetic Anhydride → Butanoic acid, 2-(ethoxymethylene)-4,4-difluoro-3-oxo-, ethyl ester

Temperature

110 °C

427.8 g of acetic anhydride (4.15 mol) were initially charged in a stirred vessel and heated to 110° C. Within 2 hours, 438 g of crude ethyl 4,4-difluoroacetoacetate from synthesis example 2 (20.9% solution in ethanol/ethyl acetate) and 145.3 g (0.96 mol) of triethyl orthoformate were metered in in parallel. After about half had been fed in, reflux set in at 106° C. At the end of the metered addition, the internal temperature was 94° C. The mixture was stirred at reflux temperature for a further 6 hours and then cooled to 25° C. At a pressure of 150 mbar, the low boilers (ethyl acetate, acetic acid, acetic anhydride, triethyl orthoformate) were distilled off at internal temperature 40-90° C. To complete the removal, the pressure was lowered to 10 mbar at 90° C., and the distillation bottoms were subsequently stirred at 95° C./10 mbar for 1 hour. The distillation residue (125.7 g) comprised 89.7% by weight of the desired ethyl 2-ethoxymethylene-4,4-difluro-3-oxobutyrate. This corresponds to an overall yield over the two synthesis stages of 84.6% based on the ethyl difluoroacetate used in working example 2.

1. temperaturereflux
2. customset in at 106° C
3. additionAt the end of the metered addition
4. customwas 94° C
5. temperatureat reflux temperature for a further 6 hours
6. temperaturecooled to 25° C
7. distillationAt a pressure of 150 mbar, the low boilers (ethyl acetate, acetic acid, acetic anhydride, triethyl orthoformate) were distilled off at internal temperature 40-90° C
8. customthe removal
9. customwas lowered to 10 mbar at 90° C.
10. distillationthe distillation
11. stirringbottoms were subsequently stirred at 95° C./10 mbar for 1 hour
12. customThis corresponds to an overall yield over the two synthesis stages of 84.6%

ORD record

ord-77058c5613684b8bb9cad3ea45d40583

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207354B2