反应详情

温度

110 °C

To a stirring mixture of lithium formate (0.30 g, 5.85 mmol) and DIPEA (0.68 mL, 3.90 mmol) in DMF (3 mL) was added acetic anhydride (0.37 mL, 3.90 mmol). After 30 min, a N2 purged solution of tert-butyl 2-(N-(4-iodobenzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate INT-36 (1.33 g, 1.95 mmol) and PdCl2(dppf) (143 mg, 0.20 mmol) in DMF (2 mL) was added and the mixture heated to 110° C. for 1 h. The reaction mixture was allowed to cool to room temperature, diluted with EA (150 mL) and washed successively with 1N HCl (200 mL) and brine (200 mL). The organics were pre-absorbed onto silica gel then purified by chromatography (EA/isohexanes+1% AcOH) to afford a crude material that was further concentrated from toluene (20 mL). The crude solid was triturated from diethyl ether/isohexanes (10 mL:100 mL) and isolated by filtration to afford 721 mg (60%) of 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)methyl)benzoic acid INT-37. LCMS-ESI (m/z) calculated for C31H31F3N2O7: 600; found 599 [M−H]−, tR=2.27 min (Method 10). 1H NMR (400 MHz, DMSO) δ 13.86 (s, 1H), 10.33 (s, 1H), 8.00-7.85 (m, 2H), 7.62 (t, J=8.5 Hz, 2H), 7.56-7.29 (m, 5H), 7.28-7.11 (m, 2H), 4.71 (s, 1H), 4.62 (s, 1H), 4.01-3.92 (m, 2H), 3.85 (s, 2H), 3.83 (s, 3H), 1.41(s, 4.5H), 1.31 (s, 4.5H).

1. temperatureto cool to room temperature
2. washwashed successively with 1N HCl (200 mL) and brine (200 mL)
3. customThe organics were pre-absorbed onto silica gel
4. customthen purified by chromatography (EA/isohexanes+1% AcOH)
5. customto afford a crude material that
6. concentrationwas further concentrated from toluene (20 mL)
7. customThe crude solid was triturated from diethyl ether/isohexanes (10 mL:100 mL)
8. customisolated by filtration