Hydrochloric Acid → 5-bromo-2-chloro-N-cyclopropylbenzamide

Temperature

0 °C

Into a flame-dried 250 mL round-bottom flask equipped with a magnetic stir bar and under N2 were added 5-bromo-2-chlorobenzoic acid (10.0 g, 42.5 mmol) and DMF (3.9 mL, 51.0 mmol) in toluene (80 mL). The sol. was cooled to 0° C., and oxalyl chloride (4.4 mL, 51.0 mmol) was added dropwise over 1 h. The resulting mixture was stirred at 0° C. for 2 h and then the volatiles were removed. The resulting crude reaction mixture was dissolved in CH2Cl2 (100 mL) and cooled to 0° C. in an ice bath. Cyclopropylamine (4.5 mL, 63.7 mmol) was added dropwise over 1 h followed by addition of DIPEA (11.8 mL, 85.0 mmol). The resulting sol. was stirred at rt for 16 h. The reaction mixture was poured into a 1 L separatory funnel containing aq. 1M HCl (600 mL). The mixture was extracted with CH2Cl2 (6×250 mL). The combined org. layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The product was crystallized from hexane/CH2Cl2 and isolated by filtration to give the title compound (8.24 g, 71%).

1. customInto a flame-dried 250 mL round-bottom flask equipped with a magnetic stir bar and under N2
2. customthe volatiles were removed
3. customThe resulting crude reaction mixture
4. temperaturecooled to 0° C. in an ice bath
5. stirringThe resulting sol. was stirred at rt for 16 h
6. additionThe reaction mixture was poured into a 1 L separatory funnel
7. extractionThe mixture was extracted with CH2Cl2 (6×250 mL)
8. washlayers were washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe product was crystallized from hexane/CH2Cl2
13. customisolated by filtration

ORD record

ord-a736c7baaed5420a9bfa95f00807ca1f

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968720B2