Chloride → HCID 22598003, compound

Participants

Reaction Steps

A mixture of the chloride, 3-(2-Chloro)ethoxy-4-difluoromethoxy-1-(triisopropylsilyloxy)methylbenzene, from Step 2 (124 g, 303 mmol), 10N NaOH (300 mL, 3.03 mol) and Bu4NHSO4 (102 g, 303 mmol) in benzene (1.3 L) was heated at 65° C. for 4.5 h. The mixture was cooled to room temperature and was partitioned with 25% aq. NH4OAc (5 mL). The aqueous phase was extracted with ether (2×) and the combined organics were washed with brine, dried (Na2SO4) and concentrated. The residual oil was dissolved in dichloromethane (1 L) and 2,6-lutidine (53 mL, 454 mmol) and cooled in an ice bath. Triisopropylsilyl triflate (98 mL, 363 mmol) was slowly added and after addition was complete, the mixture was stirred at room temperature for 3 h. The mixture was cooled to 0° C. and sat. aq. NaHCO3 (50 mL) was added. Ether (1.5 L) and 25% aq. NH4OAc (500 mL) were added and the aqueous layer was extracted with ether (2×). The combined organics were washed with brine, dried (Na2SO4) and concentrated. Flash chromatography of the residue (silica gel; hexane/ethyl acetate 98:2 to 95:5) provided 3-Ethenyloxy-4-difluoromethoxy-1-(triisopropylsilyloxy)methylbenzene (67 g).

Provenance & Evidence