Sodium Carbonate → N-Cyclopropyl-3-fluoro-5-iodo-4-methylbenzamide

N-Iodosuccinimide (3.31 g, 20 mmol) was added in portions over 3 hours to a solution of 3-fluoro-4-methylbenzoic acid (2.27 g, 20 mmol) in trifluoromethanesulphonic acid (15 mL) kept at 0° C. Subsequently, the mixture was allowed to warm to room temperature and was stirred overnight. The reaction mixture was poured into ice/water and the precipitate that formed was collected by filtration and washed with water. The solid was dissolved in ethyl acetate, the organic layer was washed with saturated aqueous sodium thiosulphate solution and brine, dried (MgSO4) and the solvent was removed under vacuum. The residue obtained was treated with thionyl chloride (20 mL) and heated at 100° C. for 2.5 hours. Excess thionyl chloride was removed in vacuo and the residue was dissolved in dichloromethane (20 mL). Sodium carbonate (3.70 g, 35 mmol) and cyclopropylamine (1.90 mL, 27 mmol) were added to the solution and the mixture was stirred at room temperature for 72 hours. The mixture was then filtered and the residue was washed with dichloromethane and ethyl acetate. The combined filtrate and washings were concentrated under vacuum and the residue was purified by flash chromatography (10:1 to 5:1 hexanes/ethyl acetate) to give the title compound (2.13 g, 45%) as a white solid.

1. customkept at 0° C
2. customthe precipitate that formed
3. filtrationwas collected by filtration
4. washwashed with water
5. dissolutionThe solid was dissolved in ethyl acetate
6. washthe organic layer was washed with saturated aqueous sodium thiosulphate solution and brine
7. dry with materialdried (MgSO4)
8. customthe solvent was removed under vacuum
9. customThe residue obtained
10. temperatureheated at 100° C. for 2.5 hours
11. customExcess thionyl chloride was removed in vacuo
12. dissolutionthe residue was dissolved in dichloromethane (20 mL)
13. stirringthe mixture was stirred at room temperature for 72 hours
14. filtrationThe mixture was then filtered
15. washthe residue was washed with dichloromethane and ethyl acetate
16. concentrationThe combined filtrate and washings were concentrated under vacuum
17. customthe residue was purified by flash chromatography (10:1 to 5:1 hexanes/ethyl acetate)

ORD record

ord-0644e368052548b48253a46e3293aaaf

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772288B2