Hydrochloric Acid → HCID 69055772, compound

HRID 520731Notes

Reaction equation

HRID 520731 reaction equation
O[C:2]([CH:4]([C:6]1[CH:15]=[CH:14][C:9]([CH2:10][CH:11]([CH3:13])[CH3:12])=[CH:8][CH:7]=1)[CH3:5])=[O:3].S(Cl)(Cl)=[O:17].N1C=CC=CC=1.Cl.[O:27]1[CH2:32][CH2:31]OCC1>ClCCl>[CH2:10]([C:9]1[CH:14]=[CH:15][C:6]([CH:4]([CH3:5])[C:2](=[O:3])[CH2:31][C:32]([OH:27])=[O:17])=[CH:7][CH:8]=1)[CH:11]([CH3:13])[CH3:12]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 3672Ibuprofen, (+-)-HCID 24386Thionyl ChlorideHCID 312751,4-Dioxane

Product 1

HCID 69055772HCID 69055772, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

(−)-ibuprofen (1.2 g, 5.8 mmol) is dissolved in dioxane (5 mL); thionyl chloride (2.36 mL) is added and the solution obtained is refluxed and left to reflux for 3 hours. After cooling to room temperature, the solvent is evaporated at reduced pressure, and the excess of thionyl chloride is eliminated, dissolving the residue twice with dioxane and evaporating the solvents under high vacuum. An oily yellow residue (1.3 g; 5.79 mmol) is obtained, which is dissolved in dry dichloromethane (2 mL) and added, by means of slow dripping and in an inert atmosphere, to a solution of 2,2-dimethyl-1,3-dioxan-2,5-dione (Meldrum's acid) (0.83 g; 5.79 mmol) and pyridine (1.12 mL; 14 mmol) in dry dichloromethane (5 mL) previously cooled to T=+5° C. with a water/ice bath. Once the additions are completed, the mixture is left for one hour at this temperature and then for another hour at room temperature. The mixture, diluted with dichloromethane is repartitioned with a 2N solution of HCl and crushed ice, under vigorous stirring for approximately 30 min. After separation of the phases, the organic phase, washed with 2N HCl (2×10 mL) and with a saturated solution of NaCl, is dried on Na2SO4 after evaporation of the solvent at reduced pressure, the residue of (R) (+)-5-[2-(4-isobutyl-phenyl)-propion-1-yl]-2,2-dimethyl-1,3-dioxan-4,6-dione ([α]D=+62°; c=1.1% CH2Cl2) without further purifications, is dissolved in methanol (14 mL); the solution is reheated to reflux for 3 hours. After cooling and evaporation of the solvent, the residue is purified by means of flash chromatography (eluent: n-hexane/ethyl ether 8:2) to yield pure methyl ester of (R) (−)-4-[(4′-isobutyl)phenyl]-3-oxopentanoic acid as a colourless oil (0.6 g; 2.28 mmol); [α]D=−192.5° (c=1; CH3OH); 1H-NMR (CDCl3): σ 7.1 (s, 4H); 3.88 (q, 1H, J=8 Hz); 3.67 (s, 3H); 3.47-3.28 (q, 2H, J=8 Hz); 2.45 (d, 2H, J=8 Hz); 1.85 (m, 1H); 1.40 (d, 3H, J=8 Hz); 0.95 (d, 6H, J=7 Hz).

Workup

  1. customthe solution obtained
  2. temperatureis refluxed
  3. waitleft
  4. temperatureto reflux for 3 hours
  5. customthe solvent is evaporated at reduced pressure
  6. dissolutiondissolving the residue twice with dioxane
  7. customevaporating the solvents under high vacuum
  8. customAn oily yellow residue (1.3 g; 5.79 mmol) is obtained
  9. additionadded, by means
  10. temperaturepreviously cooled to T=+5° C. with a water/ice bath
  11. waitfor another hour at room temperature
  12. customcrushed ice
  13. customAfter separation of the phases
  14. washthe organic phase, washed with 2N HCl (2×10 mL) and with a saturated solution of NaCl
  15. customis dried on Na2SO4
  16. customafter evaporation of the solvent at reduced pressure
  17. dissolutionthe residue of (R) (+)-5-[2-(4-isobutyl-phenyl)-propion-1-yl]-2,2-dimethyl-1,3-dioxan-4,6-dione ([α]D=+62°; c=1.1% CH2Cl2) without further purifications, is dissolved in methanol (14 mL)
  18. temperatureto reflux for 3 hours
  19. temperatureAfter cooling
  20. customevaporation of the solvent
  21. customthe residue is purified by means of flash chromatography (eluent: n-hexane/ethyl ether 8:2)

Sources & evidence

ORD record
ord-b3f7628eca7048ea883039236ad72b95
Source dataset
uspto-grants-2016_05
Patent number
US09328057B2

Reaction notes

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