m-Ethynylphenol → tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-{5-[(3-hydroxyphenyl)ethynyl]pyridin-3-yl}-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Participants

Reaction Steps

To a degassed solution of tert-butyl 4-[3-((3R)-3-{[(1S)-1-(5-bromopyridin-3-yl)-3-tert-butoxy-3-oxopropyl]carbamoyl}piperidin-1-yl)-3-oxopropyl]piperidine-1-carboxylate (example 27c, 300 mg, 0.46 mmol), copper iodide (13 mg, 70 μmol) and tetrakis(triphenylphosphine) palladium(0) (53 mg, 50 μmol) in DMF (1.5 mL) and n-butyl amine (0.68 mL) was added a solution of 3-ethynylphenol (103 mg, 0.88 mmol) in DMF (1.0 mL) over 35 minutes at 100° C. After 5 additional minutes at 100° C. the mixture was diluted with DMSO and purified by preparative HPLC to yield 289 mg of tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-{5-[(3-hydroxyphenyl)ethynyl]pyridin-3-yl}-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

Provenance & Evidence