Ethanol → 2-Chloro-5-(difluoromethoxy)phenyl-3-hydroxypropanenitrile

A 25 mL flask with a stir bar was charged with 3.0 g (13.8 mmol) of 2-(2-chloro-5-(difluoromethoxy)phenyl)ethanenitrile, 12 mL of ethanol and 1.34 mL of 37% formaldehyde solution. The mixture was stirred and a mixture of 115 μL of 40% Triton B in methanol and 38 μL of DBU was added. After a very mild exotherm, all solids dissolved. After 50 minutes at ambient temperature, the reaction was quenched by the addition of 0.5 mL of 3 N HCL. The mixture was filtered to remove floc, diluted with 2 volumes of water and extracted with butyl chloride. The extracts were water washed and stripped to an oil. This was chromatographed on 35 g of silica gel eluting with 5%→60% EtOAc in hexane to recover 2.2 g (65% yield.) of the desired product, Rf 0.18 (silica gel, EtOAc:hexane=1:4).

1. dissolutionAfter a very mild exotherm, all solids dissolved
2. customthe reaction was quenched by the addition of 0.5 mL of 3 N HCL
3. filtrationThe mixture was filtered
4. customto remove floc
5. additiondiluted with 2 volumes of water
6. extractionextracted with butyl chloride
7. washwashed
8. customThis was chromatographed on 35 g of silica gel eluting with 5%→60% EtOAc in hexane
9. customto recover 2.2 g (65% yield.) of the desired product, Rf 0.18 (silica gel, EtOAc:hexane=1:4)

ORD record

ord-149d6f03d5334896aecc9bc8233de71f

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622504B2