Triethylamine → HCID 117720490, compound

Participants

Reaction Steps

In a vial slurry 2-(2-chloro-6-cyano-phenyl)acetic acid (75.4 mg, 0.37 mmol) in acetonitrile (0.3 mL). Add triethylamine (114 μL, 0.82 mmol) and stir until the solids dissolve. Add 0-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (165 mg, 0.51 mmol) and stir at ambient temperature for 10 min. In a separate flask slurry 4-[(1S,3R)-3-(hydroxymethyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl]-2-methyl-butan-2-ol hydrochloride (102 mg, 0.34 mol) in acetonitrile (0.3 mL). Add triethylamine (227 μL, 1.63 mmol) and a precipitate forms. Stir 10 min at ambient temperature. Transfer the 2-(2-chloro-6-cyano-phenyl)acetic acid, acetonitrile, triethylamine, and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate reaction mixture from the vial to the flask containing the 4-[(1S,3R)-3-(hydroxymethyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl]-2-methyl-butan-2-ol hydrochloride, acetonitrile and triethylamine reaction mixture. Rinse with acetonitrile (0.9 mL) and stir the homogeneous reaction mixture at ambient temperature overnight. Dilute the reaction mixture with water and extract with ethyl acetate. Wash the ethyl acetate extracts with water, saturated sodium bicarbonate solution and brine. Dry the extracts over sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue by silica gel chromatography, eluting with ethyl acetate: hexanes (0-60% gradient) to give a residue. Purify by reverse phase chromatography on C18 modified silica to yield the title compound as a green oil (34 mg, 0.08 mmol): (m/z): 441.2 (M+1).

Provenance & Evidence