反应详情

温度

75 °C

Sodium hydride (12.42 g of a 60% dispersion in oil, 310 mmol) was washed with petroleum ether (×3) under nitrogen and suspended in dry DMSO (250 mL). A solution of dimethyl malonate (37.3 mL, 330 mmol) in DMSO (50 mL) was added dropwise over 35 min with water-bath cooling. t-Butyl 2-chloro-5-nitrobenzoate (20.0 g, 78 mmol) was added and the mixture stirred at 70-80° C. under nitrogen for 4 h. The red-brown solution was cooled, poured into water (300 mL), and aq. HCl (2 N, 60 mL) added slowly until the red nitronate colour was dispersed. The mixture was extracted with CH2Cl2 (×3), the extracts were dried (Na2SO4) and evaporated. Formic acid (60 mL) was added to the residue and the mixture stirred at 20° C. for 15 h then 50° C. for 7 h (when tlc analysis showed no remaining t-butyl ester). The formic acid was evaporated and the residue taken up in EtOAc and washed with aq. NaCl (×3). The organic layer was extracted with aq. NaHCO3 (×3), the aqueous phase acidified (c.HCl), and extracted with CH2Cl2 (×3). The organic phase was dried (Na2SO4), evaporated, and the residue recrystallised from benzene (two crops) to give dimethyl (2-carboxy-4-nitrophenyl)malonate as cream needles (20.27 g, 88%), mp 163-164° C. 1H NMR (CDCl3) δ8.99 (d, J=2.5 Hz, 1H, H-3), 8.44 (dd, J=8.6, 2.5 Hz, 1H, H-5), 8.4 (v br s, 1H, CO2H), 7.73 (d, J=8.6 Hz, 1H, H-6), 5.94 (s, 1H, ArCH), 3.83 (s, 6H, CO2Me); 13C NMR δ169.6, 167.8 (CO2Me, CO2H), 147.4, 141.4, 132.2, 129.7, 127.6, 126.8 (C-1,2,3,4,5,6), 54.4 (ArCH), 53.3 (OMe). Anal. Calculated for CH11NO8 : C, 48.5; H, 3.7; N, 4.7. Found: C, 48.7; H, 3.7; N, 5.0%.

1. washSodium hydride (12.42 g of a 60% dispersion in oil, 310 mmol) was washed with petroleum ether (×3) under nitrogen
2. temperaturecooling
3. temperatureThe red-brown solution was cooled
4. additionwas dispersed
5. extractionThe mixture was extracted with CH2Cl2 (×3)
6. dry with materialthe extracts were dried (Na2SO4)
7. customevaporated
8. additionFormic acid (60 mL) was added to the residue
9. stirringthe mixture stirred at 20° C. for 15 h
10. wait50° C. for 7 h (when tlc analysis showed
11. customThe formic acid was evaporated
12. washwashed with aq. NaCl (×3)
13. extractionThe organic layer was extracted with aq. NaHCO3 (×3)
14. extractionextracted with CH2Cl2 (×3)
15. dry with materialThe organic phase was dried (Na2SO4)
16. customevaporated
17. customthe residue recrystallised from benzene (two crops)