Triphenylphosphine → methyl 4-(tert-butyl)-2-(1-Boc-piperidin-4-yloxy)benzoate

Participants

Reaction Steps

Methyl 4-tert-butyl-2-hydroxybenzoate (2.04 g, 9.8 mmol) was placed in a dry 250 ml RBF along with 1-Boc-4-hydroxypiperidine (1.97 g, 9.8 mmol) and triphenylphosphine (2.57 g, 9.8 mmol). The solids were dissolved in 50 ml of dry THF; then the mixture was chilled on ice with stirring under a nitrogen atmosphere. Diisopropyl azodicarboxylate (DIAD) (1.98 g, 1.92 ml, 9.8 mmol) was added dropwise to the chilled solution over 20 min. The mixture was stirred a few minutes on ice, then allowed to warm to room temperature and left stirring overnight. The reaction mixture was concentrated in vacuo, partitioned between 200 ml each water and dichloromethane and the organic layer washed with brine, then dried over sodium sulfate and reconcentrated in vacuo. The yellow residue was dissolved in 70 ml of ether, then chilled (−10° C.) to precipitate most of the triphenylphosphine oxide. The mixture was filtered, reconcentrated and then purified on a Waters Prep 500 chromatograph (two cartridges, hexanes through 7:3 hexanes:EtOAc) to give the title product (2.41 g, 63%) as a colorless oil.

Provenance & Evidence