Oxalyl chloride → HCID 86712690, compound

Oxalyl chloride (0.891 mL, 10.2 mmol) was slowly added to a solution of 2-bromo-4-methylbenzoic acid (813 mg, 3.78 mmol) and DMF (0.16 mL) in THF (35 mL) under nitrogen. The resulting mixture was stirred at room temperature for 30 minutes, then the volatiles were removed in vacuo and the residue azeotroped with toluene (2×20 mL). The resulting residue was taken up in anhydrous acetonitrile (40 mL) and chilled to 0° C. under a nitrogen atmosphere. A solution of TMS-diazomethane (2.0 M in Et2O; 4.35 mL, 8.70 mmol) was rapidly added and the resulting mixture was stirred at room temperature for 1 hour. EtOAc (30 mL) and saturated aqueous NaHCO3 (20 mL) were added and the layers separated. The aqueous layer was extracted with EtOAc (2×30 mL), then the combined organic extracts were washed with water (×2), brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 10-20% EtOAc in petroleum benzine 40-60° C.) to give the title compound A83 as a yellow oil (667 mg, 74%); 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J=0.6 Hz, 1H), 7.36 (d, J=7.5 Hz, 1H), 7.15 (dd, J=7.8, 0.7 Hz, 1H), 5.73 (s, 1H), 2.35 (s, 3H).

1. customthe volatiles were removed in vacuo
2. customthe residue azeotroped with toluene (2×20 mL)
3. temperaturechilled to 0° C. under a nitrogen atmosphere
4. stirringthe resulting mixture was stirred at room temperature for 1 hour
5. customthe layers separated
6. extractionThe aqueous layer was extracted with EtOAc (2×30 mL)
7. washthe combined organic extracts were washed with water (×2), brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. customevaporated in vacuo
11. custompurified by column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 10-20% EtOAc in petroleum benzine 40-60° C.)

ORD record

ord-c0d4ce1b18104c269bc12ea07eec2740

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266864B2