Hydrochloric Acid → 5-Bromo-3-chloro-2-fluorobenzenemethanamine

Temperature

65 °C

To a solution of 5-bromo-3-chloro-2-fluorobenzonitrile (13.2 g, 56.3 mmol) in THF (200 mL) was added under an argon atmosphere a 1M solution of boran-tetrahydrofuran-complex (70.4 mL, 70.4 mmol) dropwise over 30 min. The reaction mixture was then heated at 65° C. for 1.5 h. After cooling to RT, a 2N HCl solution (70.4 mL, 141 mmol) was added dropwise over 30 min. The reaction mixture was then again heated at 65° C. for 1 h and subsequently cooled to RT. Volatiles were evaporated and the residue was taken up in 1M aqueous HCl solution, followed by extraction with EtOAc (3×150 mL). The combined organics were washed with 1M aqueous HCl solution. The combined acid phases were basified to pH=12 by addition of 4M aqueous NaOH solution and then extracted with EtOAc (3×150 mL). The organics were dried (Na2SO4), filtered and evaporated in vacuo to afford the title compound as a yellowish oil. MS (LC/MS): 238.0 [M+H]+; tR (HPLC conditions c): 3.25 min. The material thus obtained was used directly in the next step without further purification

1. temperatureAfter cooling to RT
2. temperatureThe reaction mixture was then again heated at 65° C. for 1 h
3. temperaturesubsequently cooled to RT
4. customVolatiles were evaporated
5. extractionfollowed by extraction with EtOAc (3×150 mL)
6. washThe combined organics were washed with 1M aqueous HCl solution
7. additionThe combined acid phases were basified to pH=12 by addition of 4M aqueous NaOH solution
8. extractionextracted with EtOAc (3×150 mL)
9. dry with materialThe organics were dried (Na2SO4)
10. filtrationfiltered
11. customevaporated in vacuo

ORD record

ord-3f39aa0dbdf2485dafb4d5eaff3804de

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085555B2