Reaktion #718031

Reaktionsgleichung

Intermediate 90a

(R)-3-[N′-(5-Fluoro-pyridin-2-yl)-hydrazinocarbonyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Ph3P

Et3N

hexachloroethane

Et3N

BOC anhydride

→

title compound

Ausbeute 73.0%

(R)-3-(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Ausbeute 73.0%

Lösungsmittel

water

THF

DCM

MeOH

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe suspension was filtered
2. 2
   Waschenthe filter-cake washed with THF (10 mL)
3. 3
   Waschenwashed with DCM-MeOH (1:1, 50 mL) and MeOH (50 mL)
4. 4
   WaschenThe product was eluted with 2M NH3 in MeOH (75 mL)
5. 5
   Einengenconcentration in vacuo
6. 6
   Sonstigegave a brown oil that
7. 7
   workup.STIRRINGThe solution was stirred at RT for 45 min
8. 8
   Extraktionthe aqueous extracted with DCM (5 mL)
9. 9
   Einengenconcentrated in vacuo
10. 10
    Sonstigeto leave a brown gum

Vorschrift

To a brown solution Intermediate 90a (1.37 g, 4.22 mmol), Ph3P (2.22 g, 8.45 mmol) and Et3N (2.35 mL, 16.9 mmol) in THF (25 mL) at 0° C. was added hexachloroethane (2.00 g, 8.45 mmol) in 3 portions at 1 min intervals. The solution was stirred at 0° C. for 30 min and at RT for 3.5 h. The suspension was filtered and the filter-cake washed with THF (10 mL). The combined organics were applied to an SCX-2 cartridge (50 g), then washed with DCM-MeOH (1:1, 50 mL) and MeOH (50 mL). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo gave a brown oil that solidified on standing. The solid was dissolved in DCM (10 mL) then Et3N (0.580 mL, 4.16 mmol) and BOC anhydride (454 mg, 2.08 mmol) added sequentially. The solution was stirred at RT for 45 min, then water (10 mL) was added and the aqueous extracted with DCM (5 mL). The combined organics were passed through a hydrophobic frit and concentrated in vacuo to leave a brown gum. FCC, using 2.5-3% MeOH in DCM, gave the title compound as a pale brown solid (933 mg, 73%). LCMS (Method 3): Rt 2.94 min, m/z 207 [MH+-C5H9O2].

Quelle