Diethyl Ether → 5-(Azetidin-1-ylcarbonyl)-2-chloropyridine

DMF (2 drops) was added to a solution of 6-chloronicotinic acid (1.00 g, 6.35 mmol) and oxalyl chloride (0.67 mL, 7.62 mmol) in DCM (20 mL) and 2M hydrogen chloride in ether (3.15 mL, 6.35 mmol). The mixture was stirred at RT for 4 hours and the DCM and excess oxalyl chloride evaporated in vacuo. The residual acid chloride was dissolved in DCM (10 mL) and added to a mixture of azetidine hydrochloride (0.66 g, 6.99 mmol) and triethylamine (2.14 mL, 13.97 mmol) in DCM (10 mL) then stirred at RT for 24 hours. The DCM was evaporated in vacuo, and the residue partitioned between ethyl acetate (100 mL) and 1M citric acid (50 mL). The ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL), dried (MgSO4), and the solvent removed in vacuo to give a residue which was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (0.73 g). 1H NMR δ (CDCl3) 2.43 (quin, 2H), 4.2-4.4 (brm, 4H), 7.42 (d, 1H), 7.97 (d, 1H), 8.63 (s, 1H). m/z 197 (M+H)+

1. customthe DCM and excess oxalyl chloride evaporated in vacuo
2. dissolutionThe residual acid chloride was dissolved in DCM (10 mL)
3. stirringthen stirred at RT for 24 hours
4. customThe DCM was evaporated in vacuo
5. customthe residue partitioned between ethyl acetate (100 mL) and 1M citric acid (50 mL)
6. washThe ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL)
7. dry with materialdried (MgSO4)
8. customthe solvent removed in vacuo
9. customto give a residue which
10. customwas chromatographed on silica
11. washeluting with a gradient of 50-100% ethyl acetate in isohexane

ORD record

ord-516f0b2594ce430392209db970a8f522

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07842694B2