2-Oxoglutaric Acid → HCID 18957384, compound

HRID 2379557Notes

Reaction equation

HRID 2379557 reaction equation
[BH3-][C:2]#N.[Na+].[NH2:5][C:6]1[CH:7]=[C:8]([OH:12])[CH:9]=[CH:10][CH:11]=1.O=[C:14]([CH2:18][CH2:19][C:20]([OH:22])=[O:21])[C:15]([OH:17])=O>CO.O=C(CCC(O)=O)C(O)=O>[OH:12][C:8]1[CH:7]=[C:6]([N:5]2[C:15](=[O:17])[CH2:14][CH2:18][CH:19]2[C:20]([O:22][CH3:2])=[O:21])[CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 512-Oxoglutaric AcidHCID 115683-AminophenolHCID 5003444Sodium cyanoborohydride

Product 1

HCID 18957384HCID 18957384, compoundYield 88.6%

Reagents, catalysts & solvents 2

HCID 512-Oxoglutaric AcidCatalystHCID 887MethanolSolvent

Procedure

NaBH3CN (11.55 g, 0.18 mol) was added to a stirred solution of 3-aminophenol (10.00 g, 0.09 mol) and 2-ketoglutaric acid (17.41 g, 0.12 mol) in MeOH (350 mL). After about 17 hours, 2-ketoglutaric acid (1.00 g, 7 mmol) was added and the mixture stirred for about 1 hour. cH2SO4 was added until pH=1 and the mixture heated to reflux. cH2SO4 (3 mL) was added after about 3 hours and then again about 1 hour later. The mixture was heated at reflux overnight, the solvent evaporated and the residue diluted with water and 10% Na2CO3 solution. The mixture was extracted with CH2Cl2, the extracts dried over Na2SO4 and concentrated to leave an oil that crystallized. This was dissolved in CH2Cl 2 containing a small amount of MeOH and diluted with hexanes to give methyl 1-(3-hydroxyphenyl)-5-oxo-2-pyrrolidinecarboxylate (18.75 g, 87%). An analytical sample was prepared by recrystallizing a 1 g sample from a mixture of CH2Cl2 and hexanes to give 0.98 g of pure material, mp 125-127° C. IR (KBr) 3200 (OH), 1730 (CO2Me), 1660 (CONH) cm-1. 1H NMR (CDCl3) δ2.16 (1H, m, CH.CH2CO), 2.40-2.70 (2H, m, CH2CO), 2.80 (1H, m, CH.CH2CO), 3.72 (3H, s, CO2CH3), 4.75 (1H, dd, J=6 Hz, J'=3 Hz, CHCO2CH3), 6.54 (1H, dd, J=8 Hz, J'=2 Hz, aromatic H), 6.68 (1H, dd, J=8 Hz, J'=2 Hz, aromatic H), 7.15 (1H, t, J=8 Hz, aromatic H meta to OH), 7.73 (1H, t, J=2 Hz, aromatic H ortho to N and OH), 8.35 (1H, bs, OH); 13C NMR (CDCl3) δ22.97, 31.11, 52.73, 61.83, 109.21, 110.78, 113.20, 129.70, 138.58, 157.38, 172.04, 175.47; MS m/z 236 (MH+).

Workup

  1. additioncH2SO4 was added until pH=1
  2. temperaturethe mixture heated to reflux
  3. additioncH2SO4 (3 mL) was added after about 3 hours
  4. customagain about 1 hour
  5. temperatureThe mixture was heated
  6. temperatureat reflux overnight
  7. customthe solvent evaporated
  8. additionthe residue diluted with water and 10% Na2CO3 solution
  9. extractionThe mixture was extracted with CH2Cl2
  10. dry with materialthe extracts dried over Na2SO4
  11. concentrationconcentrated
  12. customto leave an oil
  13. customthat crystallized
  14. dissolutionThis was dissolved in CH2Cl 2 containing a small amount of MeOH
  15. additiondiluted with hexanes

Sources & evidence

ORD record
ord-b6a2fd3e45814312b4a3259adc7b5116
Source dataset
uspto-grants-1994_11
Patent number
US05362879

Reaction notes

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