Hydrochloric Acid → HCID 68289650, compound

To a solution of the above compound (358 mg, 1.17 mmol) in tetrahydrofuran (4 mL) was added dropwise a solution of 1.67 mol/L n-butyllithium in hexane (0.84 ml, 1.41 mmol) at −78° C. under argon atmosphere. The mixture was stirred at the same temperature for 90 minutes, and then thereto was added a solution of N-fluorobenzene sulfonimide (553 mg, 1.76 mmol) in tetrahydrofuran (6 mL). The reaction solution was slowly warmed to room temperature, and stirred overnight. To the reaction solution was added water, and the mixture was extracted with ethyl acetate twice. The organic layer was combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0→19:1) to give an about 1:1 mixture of 3-fluoro-5-[(methoxymethoxy)methyl]-2-(trifluoromethyl)thiophene and 2-[(methoxymethoxy)methyl]-5-(trifluoromethyl)thiophene. The resulting mixture was dissolved in ethanol (2 mL), and then thereto was added 6 mol/L hydrochloric acid solution (1 mL) at room temperature. The mixture was stirred at the same temperature overnight, and then the reaction solution was alkalified by the addition of saturated aqueous sodium hydrogen carbonate solution, and then extracted with ethyl acetate twice. The organic layer was combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→3:2) to give the title compound, [4-fluoro-5-(trifluoromethyl)-2-thienyl]methanol (34 mg, 15%) as a colorless and clear oil.

1. stirringstirred overnight
2. extractionthe mixture was extracted with ethyl acetate twice
3. washwashed with water and saturated brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0→19:1)
7. customto give
8. stirringThe mixture was stirred at the same temperature overnight
9. extractionextracted with ethyl acetate twice
10. washwashed with water and saturated brine
11. dry with materialdried over anhydrous sodium sulfate
12. concentrationconcentrated under reduced pressure
13. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→3:2)

ORD record

ord-06f2139a97fa40a2a031a6cf55412a4c

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987445B2