Hydrochloric Acid → HCID 22172872, compound

To a solution of sodium ethoxide in ethanol obtained from 5.95 g (0.26 mmol) of sodium and 200 ml of anhydrous ethanol, a solution of 45.1 g (0.26 mmol) of diethyl methylmalonate in 200 ml of ethanol was added dropwise, while vigorously stirring, over 15 min. Then, 64.3 g (0.24 mmol) of 2-bromo-1-(bromomethyl)-4-fluorobenzene in 50 ml of ethanol was added dropwise with such a rate, so the reaction mixture would be slowly refluxing. The resulting mixture was additionally refluxed for 4 h, then cooled to room temperature, and a solution of 51.8 g of potassium hydroxide in 150 ml of water was added. This mixture was refluxed for 3 h, and then ethanol was distilled off at atmospheric pressure. The solution obtained was cooled to ambient temperature and acidified by saturated hydrochloric acid to pH 1. The precipitate formed was filtered off, washed with 2×150 ml of cold water, and dried in air. The dibacic acid obtained was then dehcarboxylated by heating it at 160° C. for 2 h. To the viscous oil obtained, 60 ml of SOCl2 was added, and the resulting mixture was stirred for 24 h at room temperature. The excess of SOCl2 was distilled off, and the residue was dissolved in 200 ml of anhydrous dichloromethane. The solution obtained was added dropwise to a suspension of 37.7 g (0.28 mmol) of AlCl3 in 800 ml of dichloromethane for 1 h at 0° C. The reaction mixture was refluxed for 3 h, then cooled to room temperature, poured on 300 cm3 of ice, and finally acidified by saturated HCl to pH 3. The organic layer was separated, and the aqueous layer was washed with 3×200 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The title product was isolated using flash chromatography (d 50 mm, l 800 mm, eluent: hexanes-CH2Cl2, 2:1, vol.). Yield 47.3 g (81%).

1. temperatureso the reaction mixture would be slowly refluxing
2. temperatureThe resulting mixture was additionally refluxed for 4 h
3. temperatureThis mixture was refluxed for 3 h
4. distillationethanol was distilled off at atmospheric pressure
5. customThe solution obtained
6. temperaturewas cooled to ambient temperature
7. customThe precipitate formed
8. filtrationwas filtered off
9. washwashed with 2×150 ml of cold water
10. customdried in air
11. customThe dibacic acid obtained
12. temperatureby heating it at 160° C. for 2 h
13. customTo the viscous oil obtained
14. stirringthe resulting mixture was stirred for 24 h at room temperature
15. distillationThe excess of SOCl2 was distilled off
16. dissolutionthe residue was dissolved in 200 ml of anhydrous dichloromethane
17. customThe solution obtained
18. temperatureThe reaction mixture was refluxed for 3 h
19. temperaturecooled to room temperature
20. customThe organic layer was separated
21. washthe aqueous layer was washed with 3×200 ml of methyl-tert-butyl ether
22. dry with materialThe combined organic fractions were dried over K2CO3
23. customevaporated to dryness

ORD record

ord-280f207c7cc046fbb0a11daf9fed5615

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07446216B2