Diisopropylamine → 3-[(2,5-Dichloropyridin-4-yl)(hydroxy)methyl]-4-fluorobenzonitrile

Diisopropylamine (0.52 ml, 3.70 mmol) was dissolved in tetrahydrofuran (5 ml). At −78° C., a hexane solution (1.54M, 2.20 ml, 3.39 mmol) of n-butyl lithium was added dropwise to the resulting solution. The reaction mixture was stirred at the same temperature for 30 minutes. A tetrahydrofuran solution (20 ml) of 2,5-dichloropyridine (0.46 g, 3.08 mmol) was added dropwise to the reaction mixture. After stirring further at the same temperature for 1 hour, a tetrahydrofuran solution (5 ml) of 5-cyano-2-fluorobenzaldehyde (0.46 g, 3.08 mmol) was added dropwise to the reaction mixture. The resulting mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layers were combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue thus obtained was subjected to silica gel chromatography. The fraction obtained from the n-hexane:ethyl acetate=10:2 eluate was concentrated under reduced pressure to give the title compound (0.68 g, 2.28 mmol, 74%) as a pale yellowish brown oil.

1. stirringAfter stirring further at the same temperature for 1 hour
2. stirringThe resulting mixture was stirred at the same temperature for 30 minutes
3. extractionfollowed by extraction with ethyl acetate
4. dry with materialdried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationThe filtrate was concentrated under reduced pressure
7. customThe residue thus obtained
8. concentrationethyl acetate=10:2 eluate was concentrated under reduced pressure

ORD record

ord-429516830b1840efa15846eea46fea24

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07932271B2