Tetrahydrofuran → 5-Cyclopropyl-2-ethoxy-6-(4-fluorophenyl)nicotinaldehyde

A THF (20 mL) solution of ethyl 5-cyclopropyl-2-ethoxy-6-(4-fluorophenyl)nicotinate (2.06 g) was added to a THF (20 mL) suspension of lithium aluminum hydride (237 mg) under ice cooling in a nitrogen atmosphere. After stirring at the same temperature as above for 30 minutes, water (0.20 mL) and a 15% aqueous sodium hydroxide solution (0.20 mL) were added thereto, and the mixture was stirred for 5 minutes. Then, water (0.60 mL) was further added thereto. The reaction mixture was stirred for 1 hour and then filtered. The filtrate was concentrated under reduced pressure. Manganese dioxide (5.43 g) was added to a toluene (10 mL) solution of the obtained residue, and the mixture was stirred at 60° C. for 1 hour in a nitrogen atmosphere. The reaction mixture was filtered, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (1.47 g).

1. stirringThe reaction mixture was stirred for 1 hour
2. filtrationfiltered
3. concentrationThe filtrate was concentrated under reduced pressure
4. additionManganese dioxide (5.43 g) was added to a toluene (10 mL) solution of the obtained residue
5. stirringthe mixture was stirred at 60° C. for 1 hour in a nitrogen atmosphere
6. filtrationThe reaction mixture was filtered
7. distillationthe solvent was distilled off under reduced pressure
8. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

ORD record

ord-07d2ee3a5c9843e8991ab3e02d4bdcc7

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09353108B2