4-Bromo-2-chloroaniline → HCID 58103913, compound

Temperature

68 °C

To a solution of 4-bromo-2-chloroaniline (C.A.S. 38762-41-3), (1 g, 4.843 mmol) in AcOH (19 ml) and MeOH (10 mL) was added [(1-ethoxycyclopropyl)oxy]-trimethylsilane (1.199 ml, 5.57 mmol) dropwise at r.t. The reaction mixture was then refluxed at 67-69° C. for 3 h. under a N2 atmosphere. The mixture was then concentrated in vacuo to obtain a crude oil. Into a 200 mL four-necked flask fitted with a reflux condenser, a mechanical stirrer and a thermometer were added NaBH4 (0.366 g, 9.687 mmol) and anhydrous THF (10 mL). After cooling to 5° C., BF3.Et2O complex (1.228 ml, 9.687 mmol) was added dropwise and the mixture stirred under a N2 atmosphere at 5° C. for 1 h. The crude oil dissolved in THF (5 mL), was added dropwise at 5-10° C. over 20 min. After stirring at r.t. for 5 h, at reflux for 2 h. and then removing THF by distillation, the mixture was cooled to r.t. and poured into water. The resulting mixture was extracted with Et2O. The Et2O layer was washed with water and dried (Na2SO4) followed by the removal of Et2O in vacuo. The crude product thus obtained was purified by column chromatography (silica gel; Heptane/AcOEt 99:1 as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D34 (0.390 g, 32.6%).

1. concentrationThe mixture was then concentrated in vacuo
2. customto obtain a crude oil
3. customInto a 200 mL four-necked flask fitted with a reflux condenser, a mechanical stirrer
4. temperatureAfter cooling to 5° C.
5. additionBF3.Et2O complex (1.228 ml, 9.687 mmol) was added dropwise
6. additionwas added dropwise at 5-10° C. over 20 min
7. stirringAfter stirring at r.t. for 5 h
8. temperatureat reflux for 2 h.
9. distillationremoving THF by distillation
10. temperaturethe mixture was cooled to r.t.
11. additionpoured into water
12. extractionThe resulting mixture was extracted with Et2O
13. washThe Et2O layer was washed with water
14. dry with materialdried (Na2SO4)
15. customfollowed by the removal of Et2O in vacuo

ORD record

ord-8e7959050d8d4eaaa9ef6ed7184bef30

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716480B2