Hydrochloric Acid → N-(4-chloro-2-fluoro-3-iodophenyl)acetamide

Temperature

-65 °C

To a solution of N-(4-chloro-2-fluorophenyl)acetamide prepared above (12.0 g, 64 mmol) in THF (300 mL) at −78° C. is added dropwise n-BuLi (2.0 M in cyclohexane, 64 mL, 128 mmol) keeping the reaction temperature below −60° C. The reaction mixture is stirred between −60 to −70° C. for 2 hours and 1,1,1-trifluoro-2-iodoethane (20.1 g, 96 mmol) is added dropwise at −78° C. The mixture is stirred at this temperature for additional 3 hrs. Then a 1N HCl (200 mL) solution is added slowly at −78° C. The mixture is allowed to warm to room temperature and extracted with EtOAc (200 mL×3). The combined organic layers are washed with water and brine, then dried over MgSO4. The solvent is removed and the residue is stirred in ether and hexanes (1:2, 120 mL) for 1 hour. The solid is filtered to give N-(4-chloro-2-fluoro-3-iodophenyl)acetamide.

1. customthe reaction temperature below −60° C
2. stirringThe mixture is stirred at this temperature for additional 3 hrs
3. temperatureto warm to room temperature
4. extractionextracted with EtOAc (200 mL×3)
5. washThe combined organic layers are washed with water and brine
6. dry with materialdried over MgSO4
7. customThe solvent is removed
8. stirringthe residue is stirred in ether
9. waithexanes (1:2, 120 mL) for 1 hour
10. filtrationThe solid is filtered

ORD record

ord-af123905633b4a3489aa6a550c17e8d9

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362294B2