Hydrochloric Acid → 3-fluoro-2-methylthio-4-trifluoromethylbenzoic Acid

25.0 g (120.1 mmol) of 3-fluoro-4-trifluoromethylbenzoic acid were dissolved in 250 ml of dry tetrahydrofuran (THF), and 100.9 ml of n-butyllithium (2.5 M in hexane, 252.3 mmol) were added dropwise at −40° C. The mixture was stirred for 3 h, and a solution of 32.5 ml (360.4 mmol) of dimethyl disulfide in 50 ml of dry THF was then added dropwise. The mixture was stirred for 16 h, during which process, after half an hour, the temperature climbed slowly to RT. For work-up, 2 M HCl was added carefully. The mixture was extracted with diethyl ether, and the organic phase was subsequently extracted with 2 M NaOH. The aqueous phase was acidified and extracted with diethyl ether. The organic phase was washed with water, dried, and the solvent was removed in vacuo. The residue was stirred with n-heptane and the solid was separated off by a filtration. This gave 17.0 g of crude product, which was employed in the next synthesis step without further purification.

1. stirringThe mixture was stirred for 16 h, during which process, after half an hour
2. customclimbed slowly to RT
3. extractionThe mixture was extracted with diethyl ether
4. extractionthe organic phase was subsequently extracted with 2 M NaOH
5. extractionextracted with diethyl ether
6. washThe organic phase was washed with water
7. customdried
8. customthe solvent was removed in vacuo
9. stirringThe residue was stirred with n-heptane
10. customthe solid was separated off by a filtration
11. customThis gave 17.0 g of crude product, which was employed in the next synthesis step without further purification

ORD record

ord-bfdcaa7ae5c04f4aa34edae872076050

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188009B2