Example 4
A PTFE bottom reactor was charged with 2 Kg of compound 12a, and 2.1 Kg of concentrated sulfuric acid was added. Then the mixture was heated with stirring for about 4 hours at 45-55° C. (30% aq NaOH scrubber was used to absorb HF generated in the reaction). The mixture was then added dropwise to ice water (5 kg/5 kg). Quench temperature was maintained at 0° C. The organic phase was separated and the aqueous layer was extracted with DCM (2L, 1 V) once. The organic layers were combined together and DCM was removed under vacuum. The crude sample was purified by vacuum distillation. Main fraction of compound 12b was collected at 62-66° C./20 mmHg. 1H NMR (400 MHz, CDCl3): δ=3.89 ppm (s, 6H); 13C NMR (100 MHz, CDCl3): δ=53.95 ppm (—CH3), 105.98 ppm (—CF2—, 1JCF 259.1 Hz), 160.94 ppm (—CO—, 2JCF 30.9 Hz); 19F NMR (188 MHz, CDCl3): δ=−112.05 ppm (s, 2F).
