Dimethylformamide → 5-Bromo-2-fluoro-4-(hydroxymethyl)benzaldehyde

Temperature

-78 °C

Tetramethylpiperidine (0.68 g, 4.87 mmol) was dissolved in tetrahydrofuran (4.5 mL). To the resultant solution was added n-butyllithium (1.0 M n-hexane solution, 4.88 mL) at 0° C., and the solution was then stirred for 15 minutes. The solution was cooled to −78° C., and a solution of (2-bromo-5-fluorophenyl)-methanol (0.50 g, 2.43 mmol) in tetrahydrofuran (2.5 mL) was added dropwise. The temperature of the solution was raised over 2 hours to −40° C. The solution was again cooled to −78° C., and N,N-dimethylformamide (0.47 mL, 6.07 mmol) was added thereto. The temperature of the solution was raised to room temperature, and the solution was then stirred for 30 minutes. Saturated aqueous ammonium chloride was added, and the resultant mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure, to thereby obtain the titled compound (604.3 mg, quantitative).

1. temperatureThe temperature of the solution was raised over 2 hours to −40° C
2. temperatureThe solution was again cooled to −78° C.
3. temperatureThe temperature of the solution was raised to room temperature
4. stirringthe solution was then stirred for 30 minutes
5. extractionthe resultant mixture was extracted with ethyl acetate
6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure

ORD record

ord-f40641d84fb74929ad904fe03f5c0e41

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207134B2