Hydrochloric Acid → 2-(1,3-Dimethoxy-1,3-dioxopropan-2-yl)-5-nitrobenzoic acid

HRID 1603035Notes

Reaction equation

HRID 1603035 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].Cl[C:11]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:12]=1[C:13]([O:15]C(C)(C)C)=[O:14].Cl.[N+](=C)([O-])[O-]>CS(C)=O.O>[C:13]([C:12]1[CH:20]=[C:21]([N+:24]([O-:26])=[O:25])[CH:22]=[CH:23][C:11]=1[CH:2]([C:1]([O:8][CH3:9])=[O:7])[C:3]([O:5][CH3:6])=[O:4])([OH:15])=[O:14]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7943Dimethyl malonateHCID 10729867Tert-butyl 2-chloro-5-nitrobenzoateHCID 178486260Methanenitronate

Product 1

HCID 108039332-(1,3-Dimethoxy-1,3-dioxopropan-2-yl)-5-nitrobenzoic acidYield 88%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

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%.

Workup

  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)

Sources & evidence

ORD record
ord-82cb05b4b1344d9ba4ed464adea72bae
Source dataset
uspto-grants-1999_11
Patent number
US05985909

Reaction notes

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