Sodium Hydroxide → HCID 58286949, compound

Participants

Reaction Steps

2-({[(S)-Cyclobutyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-methyl)-4,6-difluoro-benzoic acid (3.4 g, 9.0 mmol in acetic anhydride (60 mL) was stirred at 100° C. overnight then evaporated and co-evaporated with toluene twice in vacuo to give a mixture of 4-acetyl-3-{[(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amino}-6,8-difluoro-2-benzopyran-1-one and 6,8-difluoro-3-methyl-1-oxo-1H-2-benzopyran-4-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide. The obtained residue was dissolved in tetrahydrofuran (15 mL), allowed to cool on an ice-water bath and 2M aqueous NaOH (18 mL) was added. The cold bath removed and the reaction mixture was stirred for 30 min. The obtained mixture was diluted with water (20 mL) and extracted with isopropyl acetate (40 mL) which was washed with water (40 mL). The combined aqueous phase was cooled on ice bath and the pH was adjusted to 1 with conc. HCl. The title product was separated by extraction with isopropylacetate (2×40 mL) and purified by flash chromatography (50 g SiO2, the product was eluted with 1:1 ethyl acetate-heptane, 1.58 g, yield 42%). LC-MS (m/z) 420.6 (MH+); tR=1.35.

Provenance & Evidence