5-(tert-butoxy)picolinonitrile synthesis

Yield:1392467-08-1 62%

Reaction Conditions:

in N,N,N,N,N,N-hexamethylphosphoric triamide;N,N-dimethyl-formamide;

Steps:

1 5-tert-Butoxypicolinic acid Step 1:

To NaOtBu (1.57 g, 16.4 mmol) in HMPA (6 mL) was added DMF (6 mL) (to facilitate stirring). 5-Fluoropyridine-2-carbonitrile (1.00 g, 8.19 mmol) was added and the dark mixture was stirred overnight. The mixture was diluted with water (100 mL), extracted with DCM (3×50 mL) and the organics were washed with water (50 mL) and sat. aq. NaHCO₃ (50 mL), dried over MgSO₄, evaporated and purified by column chromatography (0-50% EtOAc/hex) to give 5-tert-butoxypyridine-2-carbonitrile (0.90 g, 62%) as a yellow solid. ESI-MS m/z calc. 211.1. found 211.9 (M+1)+; Retention time: 0.97 minutes (3 min run). ¹H NMR (400 MHz, CDCl₃) δ 8.38 (dd, J=2.7, 0.5 Hz, 1H), 7.67-7.56 (m, 1H), 7.41-7.31 (m, 1H), 1.52-1.38 (m, 10H).

References:

US2012/196869,2012,A1 Location in patent:Paragraph 0420; 0421; 0422