Water → HCID 67233756, compound

2-Bromo-4-fluorobenzenamine (10 g, 52.6 mmol) was weighed into a round bottom flask, and dissolved in 40 mL of 6N HCl. The reaction mixture was then heated to reflux, followed by drop-wise addition of (E)-but-2-enal (4.578 mL, 55.3 mmol) mixed with 1.0 mL deionized water over 25 minutes. Following complete addition the reaction was heated at 100° C. for an additional 35 minutes, until all the 2-bromo-4-fluorobenzenamine had been consumed. The reaction was cooled to ambient temperature, followed by addition of 50 mL of Et2O. The reaction was stirred for 5 minutes followed by removal of Et2O by partitioning. The aqueous layer was replaced into the original reaction flask and ZnCl2 (3.586 g, 26.3 mmol) was then added in two portions followed by cooling to 0° C. over 30 minutes. The pH of the crude reaction mixture was then adjusted to pH=8.0 using concentrated NH4OH. The crude mixture was then extracted with Et2O, followed by ethyl acetate. The combined organics were then dried over Na2SO4, and then concentrated in vacuo, affording the desired product as a brown solid (10.7 g, 85% yield). MS APCI (+) m/z 240.2 and 242.2 (M+1 of each Br isotope) detected.

1. temperatureThe reaction mixture was then heated
2. temperatureto reflux
3. additionmixed with 1.0 mL
4. customover 25 minutes
5. additionaddition the reaction
6. customhad been consumed
7. additionfollowed by addition of 50 mL of Et2O
8. customfollowed by removal of Et2O
9. customby partitioning
10. additionwas then added in two portions
11. temperatureby cooling to 0° C. over 30 minutes
12. customThe pH of the crude reaction mixture
13. extractionThe crude mixture was then extracted with Et2O
14. dry with materialThe combined organics were then dried over Na2SO4
15. concentrationconcentrated in vacuo

ORD record

ord-3491df3142bf40568ff5af6f4197cb42

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895550B2