Dimethylformamide → Methyl (2S)-3-[3-bromo-4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)phenyl]-2-[(tert-butoxycarbonyl)amino]propanoate

Participants

Reaction Conditions

Reaction Steps

Methyl (2S)-3-(3-bromo-4-iodophenyl)-2-[(tert-butoxycarbonyl)amino]-propanoate (2.35 g, 4.85 mmol), 2-tert-butylisothiazol-3(2H)-one 1,1-dioxide (1.61 g, 8.49 mmol), palladium acetate (218 mg, 0.971 mmol), tetra-N-butylammonium chloride (1.35 g, 4.85 mmol), and then triethylamine (2.03 mL, 14.6 mmol) were dissolved in DMF (40.0 mL, 0.516 mmol). The solution was degassed and then stirred with heating at 70° C. under nitrogen for 120 minutes. LCMS indicated an absence of starting material. The solution was diluted with ethyl acetate (150 mL) and washed with water (150 mL) and aqueous hydrochloric acid solution (1.0 N, 150 mL). The organic phase was filtered through celite with ethyl acetate washing. The organic solution was dried over sodium sulfate, concentrated in vacuo, and then purified by silica gel chromatography (slow gradient, 10–25% ethyl acetate/hexanes) to afford product as a yellow solid (1.38 g, 52%). 1H NMR (500 MHz, CD3OD): δ 7.80 (d, J=8.2 Hz, 1H), 7.55 (s, 1H), 7.23 (d, J=8.2 Hz, 1H), 6.89 (s, 1H), 5.08–5.05 (m, 1H), 4.62–4.59 (m, 1H), 3.76 (s, 3H), 3.23–3.20 (m, 1H), 3.06–3.02 (m, 1H), 1.79 (s, 9H), 1.43 (s, 9H). LCMS found for C22H29BrN2O7SNa (M+Na)+: m/z=567.

Provenance & Evidence