Sodium Hydroxide → HCID 59001094, compound

Participants

Reaction Steps

A solution of 2-(4-chlorobenzenesulfonylamino)-4-fluoro-4-methyl-pentanoic acid ethyl ester (457 mg, 1.30 mmol) in MeOH (20 mL) was treated with 10 N NaOH (780 tL, 7.8 mmol) at rt for 18 h. The crude reaction mixture was concentrated in vacuo. The residue was treated with water (50 mL) and 1 N HCl (20 mL). The aqueous solution was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo to afford a white solid containing 2-(4-chlorobenzenesulfonylamino)-4-fluoro-4-methyl-pentanoic acid. A mixture of the crude solid, 1-hydroxybenzotriazole (263 mg, 1.95 mmol), diisopropylethylamine (670 mg, 5.2 mmol), ammonium chloride (140 mg, 2.6 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (373 mg, 1.95 mmol), and DMF (20 mL) was stirred at rt for 24 h. The crude mixture was poured into water (500 mL). The aqueous solution was extracted with EtOAc/hexane (90: 10, 3×150 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude concentrate was purified using silica gel column chromatography (95:5, chlorofor/MeOH) to afford 0.426 g (100% yield) of the title compound: LCMS (M+Na)+345.3; 1H NMR (400 MHz, DMSO-d6) δ8.10 (d, 1H, J=9.2), 7.77 (d, 2H, J=8.5), 7.62 (d, 2H, J=8.9), 7.34 (s, 1H), 6.92 (s, 1H). 3.85 (m, 1H), 1.89 (m, 1H), 1.74 (m, 1H), 1.31 (d, 3H, J=21.7), 1.29 (d, 3H, J=21.9).

Provenance & Evidence