Hydrochloric Acid → 4-(4-Fluoro-3-methylphenyl)-4-oxobutanoic acid

Temperature

62 °C

To an oven dried three neck flask was added Mg turnings (355 mg, 14.6 mg-at.) catalytic amount of iodine, and 20 mL THF. To the resulting mixture was added dropwise 4-bromo-1-fluoro-2-methyl-benzene (1.0 g, 0.005 mol) with heating to ˜62° C. After completing the addition of the aryl bromide, the mixture was stirred for an additional 30 min at 62° C. The THF solution of the prepared aryl magnesium bromide was cooled to −70° C. and succinic anhydride (1.0 g, 0.01 mmol) added as a solution in 10 mL THF. The mixture was vigorously stirred with warming to rt over 3 h and then hydrolyzed by the addition of 30 mL of 1M HCl. The resulting mixture was extracted with ethyl acetate (2×20 mL). The combined organic layers were extracted with 5% aqueous K2CO3 (3×10 mL) and the combined aqueous layers acidified with 1M HCl to pH3. A milky colloidal suspension was extracted with ethyl acetate (3×30 mL) and the combined organic layers washed with brine (2×20 mL). The solvent was evaporated under reduced pressure and the crude product used directly in the next step without further purification.

1. customTo an oven dried three neck flask
2. additionwas added Mg turnings (355 mg, 14.6 mg-at.) catalytic amount of iodine, and 20 mL THF
3. stirringThe mixture was vigorously stirred
4. temperaturewith warming to rt over 3 h
5. extractionThe resulting mixture was extracted with ethyl acetate (2×20 mL)
6. extractionThe combined organic layers were extracted with 5% aqueous K2CO3 (3×10 mL)
7. extractionA milky colloidal suspension was extracted with ethyl acetate (3×30 mL)
8. washthe combined organic layers washed with brine (2×20 mL)
9. customThe solvent was evaporated under reduced pressure
10. customthe crude product used directly in the next step without further purification

ORD record

ord-ba5ed82a434b47c9b4f9043b8e914ebb

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08119692B2