2-Methyl-3-butyn-2-ol → HCID 86627034, compound

To 30 ml of acetonitrile solution containing 7.31 g (30.6 mmol) of 5-bromo-2-difluoromethoxyphenol obtained in Reference example 11-(a) were added 6.4 mg of cuprous chloride and 6.43 ml of 1,8-diazabicyclo[5TO 5.4.0]-7-undecene at −10° C., and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added dropwise 30 ml of acetonitrile solution containing 6.18 g (73.5 mmol) of 2-methyl-3-butyn-2-ol which further contains 7.34 ml of 1,8-diazabicyclo[5.4.0]-7-undecene and 5.05 ml of trifluoroacetic anhydride at −10° C. After completion of the dropwise addition, the mixture was stirred at the same temperature for 1.5 hours, and further at 0° C. for 2 hours. After completion of the reaction, water was added to the reaction mixture, and extracted with toluene. The organic layer after separation was washed successively with 2N hydrochloric acid, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; hexane:ethyl acetate=9:1 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 4.88 g of the title compound as a colorless oil. (Yield: 52%)

1. customobtained in Reference example 11-(a)
2. customat −10° C
3. additionAfter completion of the dropwise addition
4. stirringthe mixture was stirred at the same temperature for 1.5 hours
5. waitfurther at 0° C. for 2 hours
6. additionwas added to the reaction mixture
7. extractionextracted with toluene
8. customThe organic layer after separation
9. washwas washed successively with 2N hydrochloric acid
10. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate
11. concentrationconcentrated under reduced pressure
12. additionthe fractions containing the desired compound
13. concentrationwere concentrated under reduced pressure

ORD record

ord-ccc32971b0974670b6dcee7fe338d7d9

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450319B2