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

Temperature

0 °C

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].

1. filtrationThe suspension was filtered
2. washthe filter-cake washed with THF (10 mL)
3. washwashed with DCM-MeOH (1:1, 50 mL) and MeOH (50 mL)
4. washThe product was eluted with 2M NH3 in MeOH (75 mL)
5. concentrationconcentration in vacuo
6. customgave a brown oil that
7. stirringThe solution was stirred at RT for 45 min
8. extractionthe aqueous extracted with DCM (5 mL)
9. concentrationconcentrated in vacuo
10. customto leave a brown gum

ORD record

ord-bccd63bc4e964b8a8332110607a13306

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08907094B2