ChemicalBook CAS DataBase List 4-bromo-2,5-difluorobenzoic acid

4-bromo-2,5-difluorobenzoic acid synthesis

4synthesis methods

Product Name:4-bromo-2,5-difluorobenzoic acid
CAS Number:28314-82-1
Molecular formula:C7H3BrF2O2
Molecular Weight:237

Freshly titrated n-butyl lithium (27.0 ml, 1.39 M in hexanes) is added slowly (over about 30 minutes) to a -78°C solution of diethyl ether (90 ml) containing 1,4-dibromo-2,5-difluorobenzene (10.22 g, 0.038 mol). The resulting yellow solution is stirred at -78°C for 2 hours to give a yellow suspension. Several pellets (~10) of dry ice are added to the suspension, which is then allowed to warm slowly to room temperature as it degasses (approximately 40 minutes). The resulting suspension is acidified with a 1 M aqueous solution of hydrochloric acid (500 ml), and the product extracted with diethyl ether (5 x 200 ml). The combined organics are washed with water (4 x 100 ml) and filtered. The ether solution is concentrated to approximately 200 ml under reduced pressure, and the product extracted into a saturated aqueous solution of sodium bicarbonate (3 x 200 ml). The combined aqueous extracts are washed with methylene chloride (3 x 100 ml) and acidified with hydrochloric acid. The product is extracted with diethyl ether (3 x 200 ml), and the combined organic extracts washed with water (2 x 200 ml), dried over magnesium sulfate, and concentrated under reduced pressure to give 4-Bromo-2,5-difluorobenzoic acid as a pale yellow solid.

Figure Synthesis of 4-Bromo-2,5-difluorobenzoic acid

124-38-9
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327-51-5 Synthesis

327-51-5
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28314-82-1
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Yield:28314-82-1 97%

Reaction Conditions:

Stage #1:1,4-dibromo-2,5-difluorobenzene with n-butyllithium in diethyl ether;hexane at -78; for 2 h;Inert atmosphere;
Stage #2:carbon dioxide in diethyl ether;hexane at 20; for 1 h;

Steps:

58.a (a) 4-bromo-2,5-difluorobenzoic acid
(a) 4-bromo-2,5-difluorobenzoic acid To a 780C solution of 1,4-dibromo-2,5-difluorobenzene (2.72 g, 9.99 mmol) in dry Et20 (30 mL) under an inert atmosphere was added 2.5 M n-butyllithium solution in hexanes (4 mL, 9.99 mmol) drop-wise and the mixture left stirring for 2 h. Crushed CO2 pellets were added slowly and the mixture was allowed to warm to ambient temperature and left stirring for 1 h. After quenching with 1M aqueous HCI (10 mL) the mixture was basified with 1M aqueous NaOH (70 mL) and then washed with Et20 (2 x 50 mL). The aqueous layer was acidified with 1M aqueous HCI (80 mL) and extracted with Et20 (3 x 100 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, filtered and solvent was removed in vacuo to give 4-bromo-2,5-difluoro benzoic acid (2.3 g, 97 %) as an off-white solid, which was used without further purification.1H NMR (Method B) (CDCI3): O ppm 9.50 (brs, 1H), 7.78 (dd, J= 8.2, 6.1 Hz, 1H), 7.46 (dd, J= 9.3, 5.4 Hz, 1H); LC-MS (Method C) 234.9/236.9 [M-H] RT 3.43 mm

References:

REDX PHARMA PLC;RATCLIFFE, Andrew;HUXLEY, Anthony;LYTH, David;NOONAN, Gary;KIRK, Ralph;UOSIS-MARTIN, Mario;STOKES, Neil WO2015/155549, 2015, A1 Location in patent:Page/Page column 105; 106

FullText

Benzoic acid, 4-bromo-2,5-difluoro-, 1,1-dimethylethyl ester

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28314-82-1
142 suppliers
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References

124-38-9
122 suppliers
$175.00/23402

28314-82-1
142 suppliers
$6.00/250mg

References

327-51-5 Synthesis

327-51-5
277 suppliers
$5.00/5g

28314-82-1
142 suppliers
$6.00/250mg

References

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