Methanol → (+)-Flurbiprofen

HRID 1489393Notes

Reaction equation

HRID 1489393 reaction equation
[CH3:1][CH:2]([C:16]([OH:18])=[O:17])[C:3]1[CH:4]=[CH:5][C:6]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[C:7]([F:9])[CH:8]=1.CO.S(=O)(=O)(O)O>C(OCC)(=O)C.O>[CH3:1][C@H:2]([C:16]([OH:18])=[O:17])[C:3]1[CH:4]=[CH:5][C:6]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[C:7]([F:9])[CH:8]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 3394Flurbiprofen

Product 1

HCID 72099(+)-Flurbiprofen

Reagents, catalysts & solvents 1

HCID 22728543Water ethylacetateSolvent

Procedure

A sample of 6.2 g (25 mmol) of R,S flurbiprofen was combined with 40 g of methanol and stirred until dissolved. The solution was treated with 3.14 g (21 mmol) of cis (1R,2S)-1-aminoindan-2-ol, seeded with a small amount of (1R,2S)-1-aminoindan-2-ol (S)-flurbiprofen diastereomer, and allowed to crystallize over a period of 17 hours at ambient temperature. The mixture was then cooled and held at 4° C. for 5 hours. The solids were isolated by filtration, washed with 35 mL methanol, and dried to afford 3.8 g (38M % yield) of white crystals. The acid was released by dissolving the solid in 200 mL of an ethyl acetate-water (50/50; v/v) mixture and treating the solution with 3 g of 5N aqueous sulfuric acid. After mixing, the aqueous phase was decanted and the organic phase washed twice with 100 mL of water. The organic phase was then evaporated under vacuum. The weight of the solid residue was 2.1 g. The rotation [α]D of this solid was -18.8 (c=1, ethanol) corresponding to (S)-flurbiprofen of 44.6% enantiomeric excess.

Workup

  1. dissolutionuntil dissolved
  2. customto crystallize over a period of 17 hours at ambient temperature
  3. temperatureThe mixture was then cooled
  4. customThe solids were isolated by filtration
  5. washwashed with 35 mL methanol
  6. customdried
  7. customto afford 3.8 g (38M % yield) of white crystals
  8. additionAfter mixing
  9. customthe aqueous phase was decanted
  10. washthe organic phase washed twice with 100 mL of water
  11. customThe organic phase was then evaporated under vacuum

Sources & evidence

ORD record
ord-890945456e364627a866bd76d872ebb5
Source dataset
uspto-grants-1997_10
Patent number
US05677469

Reaction notes

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