5-Bromo-2-chlorobenzoyl chloride

8.00 kg 2-chloro-5-bromobenzoic acid was suspended in 80.00 L methylene chloride (KF of methylene chloride <0.1percent H2O) and 0.02 L of DMF added at 20 C. 5.18 Kg oxalyl chloride were slowly added and the internal temperature maintained below 25 C. The addition was slightly exothermic; gas evolution of HCl and CO2 occurred. The reaction was run at 20-25 C. overnight; a clear solution was obtained. The mixture was concentrated in vacuum to an oily residue and degased at 40 C. in vacuum. Yield of 2-chloro-5-bromobenzoic acid chloride: 8.63 kg (33.98 mol, yield 100.0percent)5-bromo-2-chlorobenzoic acid 9a (120 g, 0.51 mol) was dissolved in dichloromethane (500 mL) and cooled under nitrogenTo a solution of oxalyl chloride (86 mL, 1000 mmol) and N, N-dimethylformamide (2.5 mL, 32 mmol) was added dropwise to -5 ° C, The reaction was stirred at room temperature for 5 hours. Concentration under reduced pressure gave the title compound 9b as a yellow oil (131 g, 100percent).5g of 2-chloro-5-bromobenzoic acid and 30mL of dichloromethane were added into a 100mL reaction flask under nitrogen atmosphere, and then 0.16g of N, N-dimethylformamide was added, and at the temperature of 10-15 ° C, 3.2g Oxalyl chloride, incubated at the end of the reaction dropwise 1h, and then warmed to 35-40 ° C for 2-3hrs, after the end of the reaction vacuum distillation, steamed to solvent-free fractions, and then added 30mL dichloromethane vacuum distillation, to be dried residual oxalyl chloride , Pale yellow viscous material 6.9g, namely 2-chloro-5-bromobenzoyl chloride, yield 100percent.5-Bromo-2-chlorobenzoic acid 11a (93.0 g, 395 mmol) was dissolved in dichloromethane (900 mL).Cool to -5 ° C under nitrogen, add oxalyl chloride (50 mL, 590 mmol)And N, N-dimethylformamide (1.0 mL, 12.9 mmol), and the mixture was stirred and stirred at room temperature for 4 hr.After the reaction was completed, it was concentrated under reduced pressure.The title compound 11b (107 g, yellow oil) was obtained.Yield: 100percent.To a 250 mL single-mouth bottle was added 2-chloro-5-bromobenzoic acid (Compound 2) (9.40 g, 40 mmol, 1.0 eq) and dichloromethane (70 mL).Then, thionyl chloride (8.70 mL, 120 mmol, 3.0 eq) was added and the reaction was stirred at 40 ° C for 3 hours.After completion of the reaction, it was concentrated to dryness to give 10.20 g of Compound A, yield 100percent, and used directly for the next reaction.2-chloro-5-bromobenzoic acid 0.59g (2.51mmol) in 15mL three-necked flask, 5ml of anhydrous dichloromethane, and the reaction flask is placed in ice-water, stirred for ten minutes. Then, a solution of 0.31ml (3.00mmol) of oxalyl chloride, reacted at room temperature overnight. After completion of the reaction, the solvent was evaporated to give 0.62g (2.46mmol) of a yellow solution (2), a yield of 98.13percent.Step 1. Dissolve 5-bromo-2-chlorobenzoic acid (100 g, 0.43 mol) in 500 ml of methylene chloride, catalyze the addition of 1 g of pyridine, add thionyl chloride (60.5 g, 0.51 mol) dropwise at room temperature, and heat up to 40 °C reflux 3.5 hours, The reaction was completed by TLC, and dichloromethane was concentrated under reduced pressure to obtain 104 g of 5-bromo-2-chlorobenzoyl chloride (yield: 97percent), which was used as the next step without further purification.Step 2 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 10percent 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: 94.7percent, purity: 99.12percent.

Molecular Weight:253.90
XLogP3:3.9
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:251.87443
Monoisotopic Mass:251.87443
Topological Polar Surface Area:17.1
Heavy Atom Count:11
Complexity:163
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes