Water → HCID 66731659, compound

Temperature

0 °C

Vanillylacetone (5.00 g, 25.7 mmol) was dissolved in toluene (250 mL) and 4-trifluoromethylbenzylamine (4.73 g, 27.0 mmol) was added. The mixture was maintained under an atmosphere of nitrogen and heated at reflux with removal of water by Dean-Stark distillation for 16 hours. At this time the Dean-Stark trap was removed and the reaction mixture was cooled to 0° C. on an ice bath. A solution of sodium borohydride (5 g) in methanol (100 mL) was added portion-wise over 30 minutes with vigorous stirring. When the addition was complete the mixture was heated at reflux for 16 hours. At this time the reaction mixture was cooled to room temperature and poured into saturated aqueous sodium bicarbonate solution (300 mL). The resulting mixture was concentrated by rotary evaporation and the aqueous residue was partitioned between water and chloroform. The chloroform layer was dried over anhydrous sodium sulfate and then filtered and concentrated. The product was then purified using silica gel column chromatography employing a mobile phase of 5% ammonia-methanol in chloroform. Product-containing fractions were combined and concentrated then dried under high vacuum overnight to provide a light brown oil (6.72 g, 74%). 1H NMR, 13C NMR, and Mass Spectrum of the product were substantially the same as those in Example 2, A (made by the Conditioned Extraction method).

1. temperatureThe mixture was maintained under an atmosphere of nitrogen
2. temperatureheated
3. customAt this time the Dean-Stark trap was removed
4. additionA solution of sodium borohydride (5 g) in methanol (100 mL) was added portion-wise over 30 minutes with vigorous stirring
5. additionWhen the addition
6. temperaturewas heated
7. temperatureat reflux for 16 hours
8. temperatureAt this time the reaction mixture was cooled to room temperature
9. additionpoured into saturated aqueous sodium bicarbonate solution (300 mL)
10. concentrationThe resulting mixture was concentrated by rotary evaporation
11. customthe aqueous residue was partitioned between water and chloroform
12. dry with materialThe chloroform layer was dried over anhydrous sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated
15. customThe product was then purified
16. concentrationconcentrated
17. customthen dried under high vacuum overnight

ORD record

ord-ef87b2c07a64424bb3b90496e63c6ea2

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365491B2