N-methyl-2-pyrrolidone → 1,1-Dimethylethyl 4-[(6-pentyl-8-quinolinyl)oxy]-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

1,1-Dimethylethyl 4-[(6-chloro-8-quinolinyl)oxy]-1-piperidinecarboxylate (for example, as prepared for Intermediate 6) (2.73 g, 7.5 mmol) was dissolved in a mixture of THF (55 ml), NMP (5.6 ml) and iron (III) acetylacetonate (220 mg, 0.62 mmol) were added, and the mixture was cooled to 0° C. and stirred under a nitrogen atmosphere. n-Pentyl magnesium bromide (commercially available, for example, from TCI-Europe and/or Aldrich) was added dropwise over 9 min. The stirring was continued at 0° C. for 1 h, and the reaction was then allowed to warm to room temperature with stirring overnight. The reaction mixture was treated with aqueous ammonium chloride solution and extracted with EtOAc (×3). The combined organic extracts were filtered, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica chromatography (2×100 g), eluting with 0-50% EtOAc-cyclohexane over 40 min. The relevant fractions were concentrated in vacuo to give the title compound as a yellow oil (2.2 g, 74%): LCMS RT=3.76 min, ES+ve m/z 399 [M+H]+.

Provenance & Evidence