Bis(2-bromoethyl) ether → 4-(4-(Trifluoromethyl)phenyl)tetrahydro-2H-pyran-4-carbonitrile

A solution of 4-trifluoromethylbenzyl cyanide (0.92 g, 5.0 mmol) and bis(2-bromoethyl)ether (2.3 mL, 18 mmol) in DMF (10 mL) at room temperature was treated portion wise with sodium hydride (60% in mineral oil, 0.6 g, 15 mmol) over a period of 10 mins followed by stirring at the same temperature for 1 h. The mixture was then stirred at 70° C. for 16 h. Then cooled to room temperature and the reaction mixture was quenched with slow addition of methanol. Water (100 mL) was added and the mixture was extracted with EtOAc (3×50 mL). The combined organic extracts were washed with water and brine and dried over sodium sulfate, filtered and concentrated. The concentrate was purified by column chromatography using a gradient of 5% EtOAc in hexanes to 30% EtOAc in hexanes to give the title compound (1.11 g, yield: 87%). 1H NMR (CDCl3 300 MHz): δppm 7.75 (d, 2H), 7.65 (d, 2H), 4.20-4.09 (m, 2H), 4.00-3.85 (m, 2H), 2.27-2.05 (m, 4H).

1. stirringThe mixture was then stirred at 70° C. for 16 h
2. customthe reaction mixture was quenched with slow addition of methanol
3. additionWater (100 mL) was added
4. extractionthe mixture was extracted with EtOAc (3×50 mL)
5. washThe combined organic extracts were washed with water and brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe concentrate was purified by column chromatography

ORD record

ord-3a9dfcb965514d2ba4cdf1dd44025b65

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09102591B2