Triethylamine → 4-Difluoromethyl-3-methylthio-2-hydroxybenzoic acid ethyl ester

Temperature

0 °C

60 g of ethyl 4-(methylsulphanyl)-3-oxobutanoate and 61.3 g of 4-ethoxy-1,1,1-trifluorobut-3-en-2-one were initially charged in 312 g of acetonitrile and cooled to 0° C. under nitrogen. Within 30 minutes, 17.2 g of triethylamine were added dropwise at 0° C. and then stirring of the mixture at 0° C. continued for 2 hours. The reaction was stirred at 20° C. overnight, concentrated and admixed with 265 g of 10% sodium hydroxide solution, the mixture was stirred for 1 h, and the solids were filtered off with suction, washed 3 times with 50 ml of 3.5% NaOH and dried by suction. The solids were then admixed with 250 ml of water and 250 ml of toluene, and adjusted to pH 1 with 10% HCl, and further HCl was metered in with continued stirring until the pH remains below 3. Finally, the filtered phases were separated and the water phase was extracted once more with toluene. The combined toluene phases were dried and concentrated: Yield 53.7 g (60.1% of theory). 1H NMR (CDCl3, 400 MHz): δ=11.73 ppm (1H, s), 7.95 ppm (1H, d), 7.22 ppm (1H, d), 7.11-7.25-7.39 ppm (1H, t, CHF2), 4.46 ppm (2H, q), 2.41 ppm (3H, s), 1.44 ppm (3H, t).

1. waitcontinued for 2 hours
2. stirringThe reaction was stirred at 20° C. overnight
3. concentrationconcentrated
4. stirringthe mixture was stirred for 1 h
5. filtrationthe solids were filtered off with suction
6. washwashed 3 times with 50 ml of 3.5% NaOH
7. customdried by suction
8. stirringwith continued stirring until the pH
9. customFinally, the filtered phases were separated
10. extractionthe water phase was extracted once more with toluene
11. dry with materialThe combined toluene phases were dried
12. concentrationconcentrated

ORD record

ord-4740cbe59281432bacc4847354c2f7d1

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440917B2