Hydrochloric Acid → HCID 63155594, compound

6-Methylnicotinic acid N,O-dimethylhydroxylamide (737 mg, 4.09 mmol) was dissolved in dichloromethane. To this, diisobutylaluminum hydride (a 0.98 mol/L solution in hexane, 4.60 mL, 4.50 mmol) was added dropwise under a nitrogen atmosphere at −10° C. and the mixture was stirred at the same temperature for 10 minutes. To this, water (4.60 mL) was added and the mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered through Celite and the filtrate was concentrated. The residue was purified by silica gel column chromatography (chloroform/methanol=19/1) to give a 3:1 mixture (405 mg) of 2-methyl-5-formylpyridine and 6-methylnicotinic acid N,O-dimethylhydroxylamide. The mixture was dissolved in tetrahydrofuran (8.0 mL). To this, (trifluoromethyl)trimethylsilane (593 μL, 4.01 mmol) and tetrabutylammonium fluoride (a 1.0 mol/L solution in tetrahydrofuran, 340 μL, 0.340 mmol) were added under a nitrogen atmosphere at room temperature and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture, a 1N aqueous hydrogen chloride solution (6.0 mL) was added and the mixture was further stirred for 10 minutes. Then, the reaction mixture was neutralized with a saturated sodium bicarbonate solution, and extraction with ethyl acetate was performed, followed by washing with brine and drying over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol=19/1) to give 2-methyl-5-(2,2,2-trifluoro-1-hydroxyethyl)pyridine (Compound CK) (387 mg, yield: 50%).

1. stirringthe mixture was further stirred for 10 minutes
2. extractionThen, the reaction mixture was neutralized with a saturated sodium bicarbonate solution, and extraction with ethyl acetate
3. washby washing with brine
4. dry with materialdrying over anhydrous sodium sulfate
5. customThe solvent was evaporated off under reduced pressure
6. customthe residue was purified by silica gel column chromatography (chloroform/methanol=19/1)

ORD record

ord-181714acd796427dbc04603a8b0d4cbe

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08673908B2