(Trifluoromethyl)trimethylsilane → 1,1,1-Trifluoro-3-[(benzyl)oxy]-2-{[(benzyl)oxy]methyl}-2-propanol

Temperature

0 °C

A mixture of 1,3-dibenzyloxy-2-propanone (2 g) and (trifluoromethyl)trimethylsilane (2.56 ml, 2.3 equivalents) in dichloromethane (20 ml) was stirred and cooled to 0° C. A solution of 1M tetrabutylammonium fluoride in THF (4 ml) was added dropwise over 3 minutes. Initial addition of a few drops gave an exotherm of 10° C. Throughout the addition the batch temperature was maintained below 10° C. After completing the addition the dark brown mixture was stirred at +5° C. for 5 minutes when HPLC analysis indicated the reaction to be complete. The reaction mixture was stirred for an additional 5 minutes and then washed with 1M aqueous hydrochloric acid (15 ml), saturated sodium bicarbonate (15 ml) and 1% w/v aqueous sodium chloride solution (2×15 ml). The organic extract was concentrated in vacuo to give 2.5 g of the desired product as dark oil in 99.3% yield. The NMR spectrum of the product was concordant with a reference sample.

1. additionInitial addition of a few drops
2. customgave an exotherm of 10° C
3. additionThroughout the addition the batch temperature
4. temperaturewas maintained below 10° C
5. additionthe addition the dark brown mixture
6. stirringwas stirred at +5° C. for 5 minutes when HPLC analysis
7. customthe reaction
8. stirringThe reaction mixture was stirred for an additional 5 minutes
9. washwashed with 1M aqueous hydrochloric acid (15 ml), saturated sodium bicarbonate (15 ml) and 1%
10. extractionThe organic extract
11. concentrationwas concentrated in vacuo

ORD record

ord-d03a5e6182e048cf9adc1d60e12c74e9

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08247377B2