Hydrochloric Acid → 3-(2,5-Difluoro-phenyl)-acrylic acid

Temperature

100 °C

Piperidine (2 mL, 20.2 mmol, 0.168 vol) was added to a stirred mixture of 2,5-difluorobenzaldehyde (12.07 g, 85.0 mmol, 1 wt) and malonic acid (18.28 g, 175.6 mmol, 1.51 wt) in pyridine (50 mL, 4.14 vol). The reaction mixture was heated under nitrogen and held at reflux (oil bath 100° C.) for 2 hours, effervescence was observed for about 90 minutes—initially vigorous then diminishing. The reaction mixture was then allowed to cool to 20 to 25° C. and poured into stirred 2 M hydrochloric acid (310 mL, 25.7 vol) (pH recorded as 1). The resulting precipitate was aged at 20 to 25° C. for 1 hour then filtered. The filter cake was washed with water (2×50 mL, 4.1 vol) then left to dry for a further 1 hour. The solid product was dried by dissolving it in TBME (250 mL, 20.7 vol), separating the phases and the water phase washed with TBME (100 mL, 8.3 vol). The TBME phases were combined, dried over magnesium sulphate (25 g, 2 wt), filtered and concentrated on a rotary evaporator to afford the product as a white solid (13.4 g, 85.7%).

1. temperatureThe reaction mixture was heated under nitrogen
2. temperatureto cool to 20 to 25° C.
3. additionpoured
4. waitThe resulting precipitate was aged at 20 to 25° C. for 1 hour
5. filtrationthen filtered
6. washThe filter cake was washed with water (2×50 mL, 4.1 vol)
7. waitthen left
8. customto dry for a further 1 hour
9. customThe solid product was dried
10. dissolutionby dissolving it in TBME (250 mL, 20.7 vol)
11. customseparating the phases
12. washthe water phase washed with TBME (100 mL, 8.3 vol)
13. dry with materialdried over magnesium sulphate (25 g, 2 wt)
14. filtrationfiltered
15. concentrationconcentrated on a rotary evaporator

ORD record

ord-d448afc6895344b0a4dcccbc7e4d3e87

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08852937B2