Diisopropylamine → HCID 86694136, compound

Diisopropylamine (0.9 mL, 6.42 mmol) and lithium chloride (0.120 g, 2.83 mmol) were dissolved in dry tetrahydrofuran (1 mL) under nitrogen and cooled in a dry ice bath. A solution of butyllithium (2.5 M in hexanes, 2.6 mL, 6.50 mmol) was added slowly and the reaction stirred for 10 minutes. 2-Fluoropyridine (0.5 mL, 5.81 mmol) was added dropwise and the mixture stirred for 1 hour. Cyclopropanecarboxaldehyde (0.5 mL, 6.69 mmol) was added slowly. After 30 minutes, the mixture was quenched by addition of saturated ammonium chloride (5 mL). Water (200 mL) and ethyl acetate (300 mL) were added and the phases mixed and separated. The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to ethyl acetate gradient) gave cyclopropyl(2-fluoropyridin-3-yl)methanol (0.415 g, 2.482 mmol, 42.7% yield). The alcohol was dissolved in chloroform (150 mL) and treated with manganese (IV) oxide (3.0 g, 34.5 mmol). The suspension was heated at gentle reflux for 14 hours. The crude product was purified using silica chromatography (hexane to ethyl acetate gradient) to give cyclopropyl(2-fluoropyridin-3-yl)methanone (0.270 g, 1.635 mmol, 28.1% yield) as a clear oil.

1. temperaturecooled in a dry ice bath
2. stirringthe mixture stirred for 1 hour
3. waitAfter 30 minutes
4. customthe mixture was quenched by addition of saturated ammonium chloride (5 mL)
5. additionWater (200 mL) and ethyl acetate (300 mL) were added
6. additionthe phases mixed
7. customseparated
8. dry with materialThe organic was dried with magnesium sulfate
9. customevaporated to dryness under reduced pressure
10. customPurification

ORD record

ord-4293dc58b48e4b97beed8adca4764d42

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174992B2