N,N,N',N'-Tetramethylethylenediamine → tert-Butyl 4-formyl-6-phenylpyridin-3-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

A solution of 3B (3.3 g, 12.21 mmol) in dry THF (50 mL) and TMEDA (4.6 mL, 30.53 mmol) under argon was cooled to −72° C. and treated dropwise with n-butyllithium (2.5 M in hexanes, 12.2 mL, 30.53 mmol) at such a rate so that the temperature did not exceed −65° C. Upon completion of the addition, the reaction was stirred at −72° C. for an additional 15 min and then at −20° C. for 1.5 h. The reaction was cooled again to −72° C., and N-formyl piperidine (2.7 mL, 24.4 mmol) was added while the temperature was maintained below −65° C. The mixture was allowed to stir at RT for 30 min. After this time, no starting material was detected by LC-MS. The solution was cooled to 0° C. and quenched by the addition of 1 M aqueous HCl to bring the pH to 6-8. The reaction was stirred at RT for 15 min, extracted with EtOAc (3×100 mL). The combined organics were washed with saturated NaCl, dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by silica gel (110 g) column chromatography, eluting with a gradient of EtOAc (0-60%) in hexane to give the title compound as a yellow solid (1.6 g, 44%). LC/MS (method A): retention time=2.79 min, (M+MeOH+H)+=331.

Provenance & Evidence