Methanol → 1-(3',4'-Dichloro-2-fluorobiphenyl-4-yl)cyclopropane carboxylic acid 2-hydroxy-1-hydroxymethylethyl ester

Temperature

-20 °C

1-(3′,4′-Dichloro-2-fluorobiphenyl-4-yl)cyclopropane carboxylic acid oxiranylmethyl ester (1.0 g, 2.62 mmol) was dissolved in dry DCM (25 mL), and the solution was cooled at −20° C. To this solution 2,2,2-trifluoroacetic anhydride (1.46 mL, 10.49 mmol) in dry DCM (25 mL) was added, and the reaction mixture was kept at r.t. for 2 hours. All the volatile components were removed under reduced pressure, and traces of trifluoroacetic anhydride were removed by co-evaporation with toluene (2×100 mL) to afford crude 1-(3′,4′-dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylic acid 2-(2,2,2-trifluoro-acetoxy)-1-(2,2,2-trifluoro-acetoxymethyl)ethyl ester (1.4 g, 2.368 mmol) as a colourless oil. 1-(3′,4′-Dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylic acid 2-(2,2,2-trifluoro-acetoxy)-1-(2,2,2-trifluoro-acetoxymethyl)ethyl ester (0.9 g, 1.522 mmol) was dissolved in a mixture of pentane/CH2Cl2 (3/1 v/v; 10 mL), and the solution was cooled at −20° C. To this solution, pyridine (1.231 mL, 15.22 mmol) and methanol (0.925 mL, 22.83 mmol) dissolved in a mixture of pentane/DCM (3/1 v/v; 10 mL) were added. The reaction mixture was allowed to warm to r.t. and stirred at r.t. for 1 hour and 45 minutes. The solvent was removed under reduced pressure, and the residue was dried under vacuum for 1 hour to obtain crude 1-(3′,4′-dichloro-2-fluorobiphenyl-4-yl)cyclopropane carboxylic acid 2-hydroxy-1-hydroxymethylethyl ester (0.61 g, quantitative yield) which was used as such in the next reaction.

1. additionwere added
2. temperatureto warm to r.t.
3. customThe solvent was removed under reduced pressure
4. customthe residue was dried under vacuum for 1 hour

ORD record

ord-e01d6c4b55cc481ba24752a8519b8712

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08835494B2