反应详情

温度

65 °C

Lithium isopropoxide (2M in THF) (10.4 mL, 20.8 mmol) was added to a mixture of diisopropyl 2,2′-((4-methoxyphenyl)azanediyl)diacetate (21) (2.69 g, 8.32 mmol) [prepared using the same procedure as Example B step (i) using isopropyl 2-bromoacetate] and diethyl oxalate (1.13 mL, 8.32 mmol), the mixture was stirred at 65° C. for 16 h. A further portion of lithium isopropoxide (2M in THF) (5.2 ml, 10.4 mmol) was added and the reaction stirred at 65° C. for 3 h. The reaction was quenched with acetic acid (5 mL) and the volatiles removed in vacuo, the crude product was took up in EtOAc (100 mL) and partitioned with water (100 mL), the aqueous was washed with EtOAc (2×100 mL) combined organics were washed with brine (150 mL), dried (MgSO4), filtered and solvents removed in vacuo to afford a brown oil. The crude product was recrystallised from hot i-PrOH (50 mL), to provide a white solid. The solid was purified by silica gel chromatography (12 g, 0-50% EtOAc in isohexane) to afford diisopropyl 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate (UL2-020) (21 mg, 1%) as a white solid: m/z 378 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 8.62 (s, 2H), 7.12-7.01 (m, 2H), 6.93-6.84 (m, 2H), 4.80 (sept., J=6.3 Hz, 2H), 3.78 (s, 3H), 0.95 (d, J=6.2 Hz, 12H).

1. customprepared
2. stirringthe reaction stirred at 65° C. for 3 h
3. customThe reaction was quenched with acetic acid (5 mL)
4. customthe volatiles removed in vacuo
5. custompartitioned with water (100 mL)
6. washthe aqueous was washed with EtOAc (2×100 mL)
7. washcombined organics were washed with brine (150 mL)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. customsolvents removed in vacuo
11. customto afford a brown oil
12. customThe crude product was recrystallised from hot i-PrOH (50 mL)
13. customto provide a white solid
14. customThe solid was purified by silica gel chromatography (12 g, 0-50% EtOAc in isohexane)