Sulfuric Acid → 3-(2,3,6-Trifluorophenyl)but-3-en-2-one

Temperature

0 °C

The hydroxy ketone 30 (7.69 g, 35.2 mmol) and 95% H2SO4 (26.2 mL, 492.8 mmol) were pumped at 2.3 and 9.2 mL/min respectively into the flow reactor. The temperature on mixing was controlled at 22-25° C. by placing the reactor in a water bath (21° C.). The effluent was quenched into a a mixture of cold water (106 g) and heptane/IPAc (1:1, 92 mL) in a jacketed reactor cooled at 0° C.; the internal temperature of the quench solution was ˜7° C. during the reaction. The layers in the quench reactor were separated and the organic layer was washed with 10% NaH2PO4/Na2HPO4 (1:1, 50 mL). The pH of the final wash was 5-6. Solka flock (3.85 g, 50 wt %) was added to the organic solution. The resulting slurry was concentrated and solvent-switched to heptanes at 25-30° C. The mixture was filtered, rinsed with heptanes (50 mL×1). The combined filtrates were concentrated under vacuum to give 31 as an light yellow oil (6.86 g, 90 wt %, 87% yield), which solidified in a freezer. 1H NMR (CDCl3, 400 MHz): δ 7.13 (m, 1H), 6.86 (m, 1H), 6.60 (s, 1H), 6.15 (s, 1H), 2.46 (s, 3H); 19F NMR (CDCl3, 376.6 MHz): δ −117.7 (dd, J=15.0, 1.4 Hz), −135.4 (dd, J=21.4, 1.4 Hz), −42.7 (dd, J=21.4, 15.0 Hz); 13C NMR (CDCl3, 100 MHz): δ 196.3, 155.3 (ddd, J=245, 5.1, 2.9 Hz), 147.9 (ddd, J=250, 14.5, 7.8 Hz), 147.0 (ddd, J=245, 13.4, 3.7 Hz), 137.5 (d, J=1.3 Hz), 131.7, 116.6 (ddd, J=19.9, 9.7, 1.2 Hz), 116.2 (dd, J=22.6, 16.5 Hz), 110.6 (ddd, J=24.8, 6.5, 4.1 Hz), 25.8.

1. additionThe temperature on mixing
2. customwas controlled at 22-25° C.
3. custom(21° C.)
4. customThe effluent was quenched into a
5. additiona mixture of cold water (106 g) and heptane/IPAc (1:1, 92 mL) in a jacketed reactor
6. customthe internal temperature of the quench solution was ˜7° C. during the reaction
7. customThe layers in the quench reactor were separated
8. washthe organic layer was washed with 10% NaH2PO4/Na2HPO4 (1:1, 50 mL)
9. washThe pH of the final wash
10. additionSolka flock (3.85 g, 50 wt %) was added to the organic solution
11. concentrationThe resulting slurry was concentrated
12. customat 25-30° C
13. filtrationThe mixture was filtered
14. washrinsed with heptanes (50 mL×1)
15. concentrationThe combined filtrates were concentrated under vacuum

ORD record

ord-d40019809d104ee8b6d11531d85537c7

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174989B2