反应详情

温度

120 °C

Prepared using General Procedure 21. To a stirred suspension of lithium formate (1.19 g, 22.9 mmol) in DMF (10 mL) was added DIEA (2.67 mL, 15.3 mmol) and acetic anhydride (1.44 mL, 15.3 mmol) at room temperature. After 30 min the reaction mixture was purged with N2 and a solution of tert-butyl 2-(N-(4-bromobenzyl)-4-((tert-butoxycarbonyl)amino)benzamido)acetate INT-61 (3.97 g, 7.64 mmol) and PdCl2(dppf) (0.559 g, 0.764 mmol) in DMF (5 mL) was added. The reaction mixture was heated for 1 h at 120° C. The reaction mixture was poured onto 1 M citric acid (200 mL) and extracted with EA (200 mL). The organics were washed with brine (200 mL), dried over MgSO4 and concentrated in vacuo. The crude product was purified by chromatography (1% AcOH in EA/hexanes) to afford 2.92 g (79%) of 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-((tert-butoxycarbonyl)amino)benzamido)methyl)benzoic acid INT-62 as a red-tinged foam. LCMS-ESI (m/z) calculated for C26H32N2O7: 484; found 430 [M-t-Bu+H]+, tR=2.23 min (Method 10).

1. customPrepared
2. customAfter 30 min the reaction mixture was purged with N2
3. extractionextracted with EA (200 mL)
4. washThe organics were washed with brine (200 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo
7. customThe crude product was purified by chromatography (1% AcOH in EA/hexanes)