Tetrahydrofuran → 2-(2,4-Dichlorophenyl)-4,4,4-trifluoro-3-oxobutanenitrile

Temperature

90 °C

Slurry 2,4-dichlorophenylacetonitrile (I) (5.0 g, 26.9 mmol, 186.04 g/mol) in ethyl trifluoroacetate (6.4 mL, 7.6 g, 142.08 g/mol) and add 20 mL anhydrous THF. Portionwise at ambient temperature add NaH (1.88 g, 47.1 mmol, 60% in mineral oil) over 5 min. Heat reaction to reflux (90° C. bath temperature) overnight. Evaporate to thick red-brown oil and partition between Et2O (100 mL) and H2O (60 mL). Separate layers and extract H2 O with Et2O (2×75 mL). Acidify the aqueous layer with 1.0 N HCl to pH 1 (becomes cloudy white suspension) and extract aqueous layer with CH2Cl2 (3×100 mL). Dry pooled CH2Cl2 layers over Na2SO4, filter and concentrate to yellow oil (7.5 g, 26.5 mmol). Use without further purification. LCMS=281.9 (MH+); 279.8 (M−).

1. temperatureHeat
2. customreaction
3. customEvaporate to thick red-brown oil
4. custompartition between Et2O (100 mL) and H2O (60 mL)
5. extractionSeparate layers and extract H2 O with Et2O (2×75 mL)
6. extractionextract aqueous layer with CH2Cl2 (3×100 mL)
7. customDry
8. filtrationfilter
9. customUse without further purification

ORD record

ord-3954790305cf4ef385b4c21c377b950a

Source dataset

uspto-grants-2002_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06476038B1