Diisopropylamine → 4-Bromo-2-(carboxymethyl)benzoic acid

Temperature

0 °C

To a solution of diisopropylamine (13.26 mL, 93 mmol, 4.0 equiv.) in THF (50 mL) was slowly added n-BuLi (37.2 mL, 93 mmol, 4.0 equiv.) at −78° C. The mixture was allowed to warm to 0° C. and stirred at that temperature for 5 min. The reaction was cooled back to −78° C. and to this mixture was slowly added 4-bromo-2-methylbenzoic acid (5.0 g, 23.25 mmol) and dimethyl carbonate (3.91 mL, 46.5 mmol, 2.0 equiv.) in THF (50 mL) and the mixture was stirred at −78° C. for 5 min. The dry ice bath was removed and the reaction was allowed to stir at room temperature for 4 h. Upon completion of the reaction, the mixture was quenched by the addition of 75 mL water and allowed to stir overnight. The aqueous layer was separated from the organic layer. The aqueous layer was acidified with conc. HCl until pH 2, extracted with EtOAc (2×50 mL), dried over Na2SO4, filtered and evaporated to dryness to yield a white solid. The solid was recrystallized from hot EtOAc/hexanes to yield 5.65 g of 4-bromo-2-(carboxymethyl)benzoic acid as a white solid.

1. customat −78° C
2. temperatureThe reaction was cooled back to −78° C. and to this mixture
3. stirringthe mixture was stirred at −78° C. for 5 min
4. customThe dry ice bath was removed
5. stirringto stir at room temperature for 4 h
6. customUpon completion of the reaction
7. customthe mixture was quenched by the addition of 75 mL water
8. stirringto stir overnight
9. customThe aqueous layer was separated from the organic layer
10. extractionextracted with EtOAc (2×50 mL)
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. customevaporated to dryness
14. customto yield a white solid
15. customThe solid was recrystallized from hot EtOAc/hexanes

ORD record

ord-2762f637ff5b4a8b9338f5cdc24ebe2d

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09290454B2