3-Bromopyridine → 1'-pyridin-3-ylspiro[1-azabicyclo[2.2.1]heptane-2,3'-pyrrolidine]

Temperature

0 °C

A mixture of spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine] (300 mg, 1.98 mmol), 3-bromopyridine (344 mg, 2.18 mmol), tris(dibenzylideneacetone)dipalladium(0) (54.57 mg, 0.0654 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (74.22 mg, 0.131 mmol) and potassium tert-butoxide (668.8 mg, 5.96 mmol) in dry toluene (20 mL) was heated in a sealed tube flushed with argon gas at 90° C. for 8 h. The reaction was cooled to 0° C. and the contents transferred to a 100 mL round bottom flask. The solvent was removed by rotary evaporation and the residue was dissolved in a saturated solution of NaHCO3 (10 mL) and extracted with chloroform (4×15 mL). The combined chloroform extracts were dried (K2CO3), filtered and concentrated by rotary evaporation to give a dark colored syrup. This was purified by column chromatography, using MeOH:CHCl3:NH4OH (8:2:0.01, v/v) as the eluent, to afford 350 mg (79.0%) of 1′-(3-pyridyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine] as a light brown syrup. A portion of the free base (200 mg) was converted to a hydrochloride salt, which was crystallized from isopropanol and ethanol to yield 200 mg (76%) of a light brown solid, (m.p. 232°-236° C.).

1. temperaturewas heated in a sealed tube
2. customflushed with argon gas at 90° C. for 8 h
3. customthe contents transferred to a 100 mL round bottom flask
4. customThe solvent was removed by rotary evaporation
5. dissolutionthe residue was dissolved in a saturated solution of NaHCO3 (10 mL)
6. extractionextracted with chloroform (4×15 mL)
7. dry with materialThe combined chloroform extracts were dried (K2CO3)
8. filtrationfiltered
9. concentrationconcentrated by rotary evaporation
10. customto give a dark colored syrup
11. customThis was purified by column chromatography

ORD record

ord-500b15b30b7641deabde6d48a83f0274

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07923559B2