Propargyl bromide → 6-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-4-difluoromethyl-6-methylhept-1-yn-4-ol

Temperature

40 °C

Aluminum foil (108 mg, 4.00 mmol) and mercuric chloride (ca. 1 mg, 0.01 mmol) in 3.5 mL of anhydrous THF were vigorously stirred for 20 minutes. Propargyl bromide (80% in toluene, 0.45 mL, 4.00 mmol) was added slowly (the reaction mixture became warm) and the resulting mixture was stirred at 40° C. for 1 hour. The dark gray propargyl aluminum sesquibromide solution was added to a solution of 4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1-difluoro-4-methylpentan-2-one (380 mg, 1.32 mmol) in 10 mL of anhydrous THF at 0° C. and the reaction was allowed to slowly warmed to room temperature and stirred overnight. The mixture was concentrated in vacuo, quenched with ice and water, and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulfate and concentrated in vacuo to give 420 mg of the title product as an oil (97% yield), which was used without further purification.

1. temperaturebecame warm) and the resulting mixture
2. temperatureto slowly warmed to room temperature
3. stirringstirred overnight
4. concentrationThe mixture was concentrated in vacuo
5. customquenched with ice and water
6. extractionthe aqueous layer was extracted with ethyl acetate
7. dry with materialThe combined organic extracts were dried over magnesium sulfate
8. concentrationconcentrated in vacuo

ORD record

ord-4e1b120fb21c4140a5e6a60979b151f6

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08741897B2