Reaktion #794427

Reaktionsgleichung

sodium carbonate

trifluoroacetic acid

2,2′-bipyridyl

cyclopropylboronic acid

Tert-butyl (2-chloro-5-fluoropyridin-3-yl)carbamate

Intermediate 36

Tert-butyl (2-chloro-5-fluoropyridin-3-yl)carbamate

→

2-chloro-N-cyclopropyl-5-fluoropyridin-3-amine

Ausbeute 71.4%

Lösungsmittel

1,2-Dichloroethane

ethyl acetate

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthen cooled to room temperature
2. 2
   SonstigeThe solution was evaporated to dryness under reduced pressure
3. 3
   Sonstigethe crude amine partitioned between 50% saturated sodium bicarbonate (80 mL) and ethyl acetate (60 mL)
4. 4
   TrocknenThe organic was dried with magnesium sulfate
5. 5
   Sonstigeevaporated to dryness under reduced pressure
6. 6
   Temperaturthe mixture heated at 70° C. in air
7. 7
   workup.WAITAfter 2 hours
8. 8
   Temperaturthe mixture was cooled
9. 9
   WaschenIt was washed with a mixture of saturated ammonium chloride (50 mL), water (100 mL), and ammonium hydroxide (20 mL)
10. 10
    Trocknenbefore drying with magnesium sulfate
11. 11
    Sonstigeevaporating to dryness under reduced pressure
12. 12
    SonstigePurification

Vorschrift

Tert-butyl (2-chloro-5-fluoropyridin-3-yl)carbamate (Intermediate 36) (0.500 g, 2.027 mmol) was dissolved in dichloromethane (5 mL) and treated with trifluoroacetic acid (0.5 mL). The mixture was stirred at 45° C. for 1 hour then cooled to room temperature. The solution was evaporated to dryness under reduced pressure and the crude amine partitioned between 50% saturated sodium bicarbonate (80 mL) and ethyl acetate (60 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. The solid amine intermediate was combined with anhydrous cupric acetate (0.375 g, 2.065 mmol), sodium carbonate (1.00 g, 9.43 mmol), 2,2′-bipyridyl (0.325 g, 2.081 mmol) and cyclopropylboronic acid (0.305 g, 3.55 mmol). 1,2-Dichloroethane (5 mL) was added and the mixture heated at 70° C. in air. After 2 hours, the mixture was cooled and diluted with ethyl acetate (300 mL). It was washed with a mixture of saturated ammonium chloride (50 mL), water (100 mL), and ammonium hydroxide (20 mL) before drying with magnesium sulfate and evaporating to dryness under reduced pressure. Purification using silica chromatography (hexane to ethyl acetate gradient) gave 2-chloro-N-cyclopropyl-5-fluoropyridin-3-amine (0.270 g, 1.447 mmol, 71.4% yield).

Quelle