Propargyl alcohol → (E)-4-((3,5-difluoro-4-((3,3-difluoro-1-propene-1-yl)oxy)phenoxy)difluoromethyl)-4'-propyl-1,1'-bi(cyclohexane)

Participants

Reaction Conditions

Reaction Steps

In toluene, 4-(difluoro(4′-propyl-[1,1′-bi(cyclohexane)]-4-yl)methoxy)-2,6-difluorophenol (T-1, 4.02 g, 10 mmol) prepared according to a publicly known method, propargyl alcohol (2.96 mL, 50 mmol), triethylamine (4.16 g, 30 mmol) and manganese dioxide (17.4 g, 200 mmol) were stirred at 50° C. for 14 hours. The resultant reaction suspension was allowed to cool to room temperature, and then subjected to Celite filtration, a manganese residue was washed with acetone (120 mL), and thus the resulting filtrate was concentrated. The resulting concentrated residue was dissolved into hexane, and cooled to −78° C., and a resulting deposit was sucked and taken by filtration and dried under reduced pressure to give (T-2) (4.57 g, 10 mmol) as a pale yellow solid. (T-2) contained an enal intermediate corresponding to 4.32 g (9.45 mmol, 95%) and 3-propargyloxy-2-propene-1-al corresponding to 0.25 g (0.55 mmol) (calculated from 1H-NMR). The resulting pale yellow solid (4.57 g) was dissolved in 1,2-dichloroethane (20 ml), 1,1,2,2-tetrafluoroethyl-N,N-dimethylamine (3.51 ml, 30 mmol) and a 70% hydrogen fluoride-pyridine complex (390 mL, 15 mmol) were added thereto, and the resulting mixture was heated at 70° C. for 65 hours. After completion of the reaction, the reaction mixture allowed to cool to room temperature was poured into a saturated aqueous solution of sodium hydrogencarbonate (300 mL), and extracted with chloroform (240 mL×2). Combined organic layers were dried over anhydrous magnesium sulfate, the resulting residue concentrated under reduced pressure was purified by silica gel column chromatography (elution solvent: hexane), and then the resulting white solid (2.38 g) was dissolved into hexane at room temperature and cooled to −78° C., and a precipitated crystal was sucked and taken by filtration, and then dried under reduced pressure to give 2.29 g (4.78 mmol, two steps, 47.8%) of a target compound (No. 38).

Provenance & Evidence