Ethylene Glycol → HCID 86709167, compound

To a solution of commercially available 4-fluoro-2-(trifluoromethyl)benzaldehyde (15 g, 78 mmol) in toluene (90 mL) was added ethylene glycol (21.77 mL, 390 mmol) and TsOH (0.743 g, 3.90 mmol). The mixture was then heated (under a Dean-Stark trap attached to a reflux condenser) in an oil bath at 140° C. for 4 h, about 1.4-1.5 mL of water was collected, which was close to the expected volume. TLC (20% EtOAc-hexane) showed a major, new more polar spot. The mixture is diluted with EtOAc (100 mL) and washed with water (50 mL). The organic phase is washed with water (1×50 mL) and brine (50 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (330 g ISCO column) eluting with 0-10% EtOAc-hexane gradient. The cleanest fractions with product afforded 9.83 g (51% yield): MS (ESI): m/z 237 (M+H).

1. temperatureThe mixture was then heated (under a Dean-Stark trap
2. customattached to a reflux condenser
3. customabout 1.4-1.5 mL of water was collected
4. customwhich was close to the expected volume
5. additionThe mixture is diluted with EtOAc (100 mL)
6. washwashed with water (50 mL)
7. washThe organic phase is washed with water (1×50 mL) and brine (50 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified by silica gel column chromatography (330 g ISCO column)
12. washeluting with 0-10% EtOAc-hexane gradient
13. customThe cleanest fractions with product afforded 9.83 g (51% yield)

ORD record

ord-acf771a426554a429c3b4b13ec38a82e

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08957104B2