HCID 80207810, compound → HCID 50794287, compound

Temperature

70 °C

Ethyl (2E)-4-(5-fluoro-2-nitrophenoxy)but-2-enoate (Intermediate 9, 310 g, 1.09 mol) dissolved in AcOH (1.4 L) was added dropwise during one h to a slurry of iron powder (325 mesh, 305 g, 5.47 mol) in AcOH (0.90 L) at 60° C. under nitrogen atmosphere. The temperature was kept at 60-75° C. during the addition. Upon complete addition the resulting mixture was stirred at 70° C. for 30 min before it was cooled to rt. The solids were filtered off and washed with AcOH (2.5 L). The filtrate was concentrated to dryness and the residue was dissolved in EtOAc (2.0 L). The solution was washed with citric acid (aq., 10% w/w, 2×1.0 L), Na2CO3 (10% w/w, 500 mL) and water (1.5 L). The solution was then concentrated to dryness and the obtained residue was dissolved in i-PrOAc (500 mL). Concentration to dryness once again yielded a residue which was purified by column chromatography on silica using heptane/EtOAc (4:1) as eluent. The title compound (236 g, 0.986 mol, 98% w/w, 88% yield) was obtained as an oil.

1. additionThe temperature was kept at 60-75° C. during the addition
2. additionUpon complete addition the resulting mixture
3. temperaturewas cooled to rt
4. filtrationThe solids were filtered off
5. washwashed with AcOH (2.5 L)
6. concentrationThe filtrate was concentrated to dryness
7. dissolutionthe residue was dissolved in EtOAc (2.0 L)
8. washThe solution was washed with citric acid (aq., 10% w/w, 2×1.0 L), Na2CO3 (10% w/w, 500 mL) and water (1.5 L)
9. concentrationThe solution was then concentrated to dryness
10. dissolutionthe obtained residue was dissolved in i-PrOAc (500 mL)
11. concentrationConcentration to dryness
12. customonce again yielded a residue which
13. customwas purified by column chromatography on silica

ORD record

ord-b31f8d4d686b43b69c052a8d1cf49b36

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394291B2