Diethyl Malonate → 5-Nitro-2,3-dihydro-1H-indene-2-carboxylic acid

HRID 1669100Notes

Reaction equation

HRID 1669100 reaction equation
[C:1]([O:9]CC)(=[O:8])[CH2:2][C:3](OCC)=O.[H-].[Na+].BrC[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:17]=1[CH2:25]Br.[OH-].[Na+]>CCOCC.CCOC(C)=O.CCO.C1(C)C(C)=CC=CC=1>[N+:22]([C:19]1[CH:18]=[C:17]2[C:16](=[CH:21][CH:20]=1)[CH2:3][CH:2]([C:1]([OH:9])=[O:8])[CH2:25]2)([O-:24])=[O:23]

Participants

9

Reactant 4

HCID 7761Diethyl MalonateHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 108523601,2-Bis(bromomethyl)-4-nitrobenzene

Product 1

HCID 185458885-Nitro-2,3-dihydro-1H-indene-2-carboxylic acidYield 20%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 7237O-XyleneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Diethyl malonate (9.10 mL, 60.0 mmol) was added to a stirred suspension of NaH (60% in oil, 3.02 g, 126 mmol) in dry Et2O (500 mL) at 20° C. under N2 and the mixture was stirred for 30 min. 1,2-Bis(bromomethyl)-4-nitrobenzene (118) (18.5 g, 60.0 mmol) was added and the mixture was stirred at 20° C. for 24 h. The reaction was diluted with EtOAc (200 mL) and washed with 1 M HCl. The solvent was evaporated to give a brown oil that was treated with 2 M NaOH (100 mL) in EtOH (100 mL) at 20° C. for 15 h. Most of the solvent was evaporated and DCM (300 mL) was added and the mixture was acidified with 1 M HCl. The organic fraction was dried and the solvent evaporated to give a brown solid that was suspended in xylene (200 mL) and stirred at reflux temperature for 90 min. The solvent was evaporated to give a brown oil which was purified by chromatography, eluting with a gradient (0-20%) of EtOAc/pet. ether, to give acid 119 (2.44 g, 20%) as a pale yellow solid: mp (EtOAc/pet. ether) 115-117° C.; 1H NMR δ 9.10 (br s, 1H, CO2H), 8.06-8.11 (m, 2H, H-4, H-6), 7.36 (d, J=9.0 Hz, 1H, H-7), 3.30-3.56 (m, 5H, H-1, H-2, H-3); 13C NMR δ 180.0, 149.0, 147.6, 143.1, 124.8, 122.7, 119.6, 43.3, 35.9, 35.7. Anal. calcd for C10H9NO4: C, 58.0; H, 4.4; N, 6.8. Found: C, 58.2; H, 4.5; N, 6.8%.

Workup

  1. stirringthe mixture was stirred at 20° C. for 24 h
  2. washwashed with 1 M HCl
  3. customThe solvent was evaporated
  4. customto give a brown oil that
  5. customMost of the solvent was evaporated
  6. additionDCM (300 mL) was added
  7. customThe organic fraction was dried
  8. customthe solvent evaporated
  9. customto give a brown solid that
  10. stirringstirred
  11. temperatureat reflux temperature for 90 min
  12. customThe solvent was evaporated
  13. customto give a brown oil which
  14. customwas purified by chromatography
  15. washeluting with a gradient (0-20%) of EtOAc/pet. ether

Sources & evidence

ORD record
ord-aaff727487a049659c9999e02b81e9b8
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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