Hydrochloric Acid → (5-Bromopyridin-2-yl)(pyrrolidin-1-yl)methanone

Oxalyl chloride (0.83 mL; 9.3 mmol) and DMF (1 drop) were added to a solution of 5-bromoisonicotinic acid (1.57 g; 7.75 mmol) and 4M hydrogen chloride in dioxan (1.93 mL; 7.75 mmol) in DCM (50 mL). The mixture was stirred at RT for 18 hours, the DCM removed in vacuo and the residue azeotroped with toluene (2×15 mL). The residue was and added to a solution of pyrrolidine (0.78 mL; 9.3 mmol) and triethylamine (2.6 mL; 18.6 mmol) in DCM (40 mL) and the mixture stirred at RT for 6 hours. The DCM was removed in vacuo, the residue partitioned between water (75 mL) and ethyl acetate (100 mL), the organic layer washed with brine, dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 50% ethyl acetate in iso hexane, to give the desired material (1.40 g). 1H NMR δ (CDCl3): 1.85 (m, 4H), 3.6 (m, 2H), 3.7 (s, 3H), 7.7 (d, 1H), 7.85 (s, 1H), 8.55 (s, 1H); m/z 257 (M+H)+.

1. customthe DCM removed in vacuo
2. customthe residue azeotroped with toluene (2×15 mL)
3. stirringthe mixture stirred at RT for 6 hours
4. customThe DCM was removed in vacuo
5. customthe residue partitioned between water (75 mL) and ethyl acetate (100 mL)
6. washthe organic layer washed with brine
7. dry with materialdried (MgSO4)
8. customevaporated to a residue which
9. customwas chromatographed on silica
10. washeluting with 50% ethyl acetate in iso hexane

ORD record

ord-8fbdb299507044f392daf91d1837550b

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07977328B2