Tetrabutylammonium Fluoride → tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-({[4-(2-fluoroethoxy)phenyl]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, 100 mg, 150 μmol), copper iodide (3.5 mg, 20 μmol), tetrakis(triphenylphosphine) palladium(0) (17.7 mg, 20 μmol) and {[4-(2-fluoroethoxy)phenyl]ethynyl}(trimethyl)silane (73 mg, 310 μmol) in 1,2-dimethoxyethan (0.9 mL) and n-butyl amine (0.23 mL) was added a 1 M tetra-n-butyl ammonium fluoride solution in THF (200 μL) over 15 minutes at 80° C. After 20 additional minutes at 80° C. (36 mg, mmol) was added, the mixture was diluted with water after 20 minutes and extracted with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated in vacuum. The residue was purified by preparative HPLC to yield 43 mg of tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-({[4-(2-fluoroethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

Provenance & Evidence