Hydrochloric Acid → (+)-Suprofen

HRID 1109711Notes

Reaction equation

HRID 1109711 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH:4]([CH3:18])[C:5]1[CH:10]=[CH:9][C:8]([C:11]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)=[O:12])=[CH:7][CH:6]=1.Cl>P([O-])([O-])([O-])=O>[CH3:1][O:2][C:3](=[O:19])[C@H:4]([CH3:18])[C:5]1[CH:6]=[CH:7][C:8]([C:11]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)=[O:12])=[CH:9][CH:10]=1.[CH3:18][C@@H:4]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)=[O:12])=[CH:7][CH:6]=1)[C:3]([OH:19])=[O:2]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 3642305HCID 3642305, compound

Product 2

HCID 688580(+)-SuprofenHCID 11000255HCID 11000255, compound

Reagents, catalysts & solvents 1

HCID 1061PhosphateSolvent

Conditions

Temperature
22 °C

Procedure

To 100 mg crude Candida cylindracea lipase (Sigma L1754 Type VII, 500 units/mg solid) in 4 mL 0.2M phosphate buffer, pH 7.0, was added 200 mg (±)-α-methyl-4-(2-thienylcarbonyl)benzeneacetic acid methyl ester (suprofen methyl ester). The resulting suspension was gently stirred with a magnetic stirrer for 48 hours at 22° C. The reaction mixture was acidified to pH 1.0 with 1N HCl and exhaustively extracted with ethyl acetate three times. The combined organic extract was dried over sodium sulfate and was then evaporated to dryness. The residue was chromatographed over a silica gel (MN Kieselgel 60) column (0.8×15 cm). Elution of the column with a solvent system consisting of ethyl acetate-hexane (1:5) gave unreacted (R)-α-methyl-4-(2-thienylcarbonyl)benzeneacetic acid methyl ester, [α]D25 =-54.7° (c=3.9, CHCl3), ee>0.90, and (S)-α-methyl-4-(2-thienylcarbonyl)benzeneacetic acid, [α]D25 =+43.5° (c=2.1, CHCl3), ee>0.95. The optical purity expressed as enantiomeric excess (ee) is determined by proton magnetic resonance spectroscopy of the methyl ester in the presence of the chiral lanthanide shift reagent, Eu(hfc)3.

Workup

  1. extractionexhaustively extracted with ethyl acetate three times
  2. extractionThe combined organic extract
  3. dry with materialwas dried over sodium sulfate
  4. customwas then evaporated to dryness
  5. customThe residue was chromatographed over a silica gel (MN Kieselgel 60) column (0.8×15 cm)
  6. washElution of the column with a solvent system

Sources & evidence

ORD record
ord-ec9bd23e2ecd4f518647022ec4faf3fb
Source dataset
uspto-grants-1994_06
Patent number
US05322791

Reaction notes

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