Hydrochloric Acid → 5-Bromo-2-chloro-4-fluorobenzoic acid

Temperatur

0 °C

To a solution of 2-amino-5-bromo-4-fluorobenzoic acid (14.5 g, 62.2 mmol) in concentrated hydrochloric acid (30 mL) at 0° C. was added dropwise a solution of sodium nitrate (4.72 g, 68.4 mmol) in water (15 mL). The mixture was stirred at 0° C. for 2 hours, then diluted with 1,4-dioxane (40 mL) and added dropwise to a solution of copper chloride (7.4 g, 74.4 mmol) in concentrated hydrochloric acid (25 mL) under mechanical stirring while the reaction temperature was kept below 7° C. (ice-salt bath). After the addition was complete, the mixture was stirred at 0° C. for another 1 hour. Water was added, and the precipitate was filtered. The filter cake was washed with water and dissolved in ethyl acetate. The filtrate was extracted with ethyl acetate once and washed with water and then with brine. The combined organic layers were dried over sodium sulfate and concentrated to give the crude product 28 (14.5 g, 92%), which was used for the next step without further purification. MS ESI (m/z): 251 (M−H)−.

1. stirringunder mechanical stirring while the reaction temperature
2. customwas kept below 7° C.
3. additionAfter the addition
4. stirringthe mixture was stirred at 0° C. for another 1 hour
5. filtrationthe precipitate was filtered
6. washThe filter cake was washed with water
7. dissolutiondissolved in ethyl acetate
8. extractionThe filtrate was extracted with ethyl acetate once
9. washwashed with water
10. dry with materialThe combined organic layers were dried over sodium sulfate
11. concentrationconcentrated

ORD-Eintrag

ord-3ac6d78292614ae1955d6158e89957a2

Quelldatensatz

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09061060B2