Sodium Hydroxide → 4-[(1S)-1-[[(3R)-2-(2-phenoxyethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoic acid

Participants

Reaction Conditions

Reaction Steps

Stir a mixture of methyl 4-[(1S)-1-[[(3R)-2-(2-phenoxyethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoate (41.5 g, 90.5 mmol), THF (291 mL), and 2 M aqueous sodium hydroxide (181 mL, 360 mmol) at 40° C. overnight. Concentrate under reduced pressure to remove the THF. Add water (200 mL), then wash the aqueous layer with TBME (2×200 mL). Cool the aqueous layer to 5° C. and add concentrated aqueous hydrochloric acid with stirring until the pH reaches 2 (as estimated by pH paper analysis). With stirring, allow the mixture to warm to room temperature over 30 minutes, then isolate the solids by filtration. Add the solids to water (500 mL) and heat to 80° C. for one hour. Cool the mixture to room temperature, isolate the solids by filtration, and dry the solids in a vacuum oven at 45° C. overnight. Add the solids to isopropyl acetate (300 mL) and stir vigourously for 5 h. Isolate the solids by filtration, and dry the solids under reduced pressure to furnish the title compound as a white solid (26 g, 60% yield). Mass spectrum (m/z): 445 ([M+H]+).

Provenance & Evidence