110 g |
With aluminum (III) chloride; at 25℃;Inert atmosphere; |
Oxalyl chloride (86.2 g, 0.67 moles) was added to a slurry of 5-bromo-2- chlorobenzoic acid (100 g, 0.42 moles) and a catalytic amount of N, N- dimethylformamide (5 mL) in fluorobenzene (250 mL), over about 60 minutes at 15- 25 C under nitrogen atmosphere. The mixture was stirred at 21-25 C. After completion of reaction, the reaction mass was concentrated to remove excess oxalyl chloride by distillation. The obtained residue was diluted with fluorobenzene (125 mL) and cooled to 15-25 C. Thereafter, aluminum chloride was added to the reaction mass portion-wise (64.6 g, 0.48 moles), keeping the reaction mass temperature below 25 C. After completion of the reaction, the reaction was quenched into precooled dilute hydrochloric acid at 5-25 C. After stirring the reaction mass for 60 minutes at 20-25 C, the reaction mass was extracted with methylene chloride (once with 500 mL, then with 250 mL). The combined organic layers were washed with 10% aqueous sodium hydroxide solution (250 mL), water (350 mL), and 10% aqueous sodium chloride solution (350 mL) sequentially. Thereafter, the organic layer was concentrated and obtained residue was treated with n-heptane to precipitate formula 7b as a white solid (110 g). |
17.817 g |
With aluminum (III) chloride; In dichloromethane; at 20℃; for 5h;Cooling with ice; |
5-Bromo-2-chlorobenzoic acid (14.128 g, 60 mmol) was added DCM (70 mL), DMF (0.132 g, 0.03 eq), Stir, Slowly add oxalyl chloride (5.6 ^, 1.1 called), After the drop was completed at room temperature reaction 31 , Concentrated under reduced pressure to give a pale yellow oil, DCM (70 mL) was added, Adding fluorobenzene (5.7668,169), Ice bath under the addition of 41 (: 13 (88,169), After adding 5 hours at room temperature, After TLC detection reaction was completed, Ice bath slowly add water (70mL), After stirring, The organic phase was washed with 10% NaCl (50 mL) The organic phase was concentrated under reduced pressure to give a pale yellow oil, Isopropyl alcohol (70 mL) was added, Add water (70mL), Ice bath stirring crystallization 2h, Filter, The filter cake was washed with isopropanol / water (1: 1) mixed solution (20 mL) Dried to give the compound A as a pale yellow solid, 17.817g, yield: 94.7%, purity: 99.12%. |