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) stirred at room temperature and under nitrogen atmosphere was added dropwise (1-ethoxycyclopropyloxy-trimethylsilane [C.A.S. 27374-25-0] (1.199 ml, 5.57 mmol). The reaction mixture was then refluxed at 67-69° C. for 3 h. The mixture was then concentrated in vacuo to yield intermediate D30′. In another flask, NaBH4 (0.366 g, 9.687 mmol) was suspended in THF (10 mL) and cooled to 5° C. Then, BF3.Et2O complex (1.228 ml, 9.687 mmol) was added dropwise. The resulting reaction mixture was stirred under a N2 atmosphere at 5° C. for 1 h. Then, to this mixture was added a solution of D30′ in THF (5 mL) dropwise at 5-10° C. over 20 min. After stirring at r.t. for 5 h., at reflux temperature 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 organic layer was washed with water and dried (Na2SO4) followed by the removal of the volatiles under vacuo. The crude product thus obtained was purified by column chromatography (silica gel; Heptane/EtOAc 99:1 as eluent). The desired fractions were collected and evaporated in vacuo to yield intermediate compound D30 (0.390 g, 32.6%).

1. concentrationThe mixture was then concentrated in vacuo
2. customto yield intermediate
3. temperaturecooled to 5° C
4. additionThen, BF3.Et2O complex (1.228 ml, 9.687 mmol) was added dropwise
5. customThe resulting reaction mixture
6. stirringAfter stirring at r.t. for 5 h.
7. temperatureat reflux temperature for 2 h.
8. distillationremoving THF by distillation
9. temperaturethe mixture was cooled to r.t.
10. additionpoured into water
11. extractionThe resulting mixture was extracted with Et2O
12. washThe organic layer was washed with water
13. dry with materialdried (Na2SO4)
14. customfollowed by the removal of the volatiles under vacuo

ORD record

ord-ee4b10658dc14e548aa20cdf0011cee7

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785486B2