Isopropanol → Voriconazole

HRID 1099520Notes

Reaction equation

HRID 1099520 reaction equation
[CH3:1][C@H:2]([C@@:10]([OH:25])([C:17]1[CH:18]=[CH:19][C:20]([F:24])=[CH:21][C:22]=1[F:23])[CH2:11][N:12]1[N:16]=[CH:15][N:14]=[CH:13]1)[C:3]1[N:8]=[CH:7][N:6]=[CH:5][C:4]=1[F:9].[C@@]12(CS([O-])(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)(O)[O-].[Na+].C(O)(C)C>C(OCC)(=O)C>[CH3:1][C@H:2]([C@@:10]([OH:25])([C:17]1[CH:18]=[CH:19][C:20]([F:24])=[CH:21][C:22]=1[F:23])[CH2:11][N:12]1[N:16]=[CH:15][N:14]=[CH:13]1)[C:3]1[N:8]=[CH:7][N:6]=[CH:5][C:4]=1[F:9]

Participants

5

Reactant 3

HCID 3776Isopropanol2×HCID 516892Sodium BicarbonateHCID 86626425Voriconazole (1R)-(-)-10-camphorsulfonate

Product 1

HCID 71616VoriconazoleYield 81.43%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
62.5 °C

Procedure

The wet product obtained in Example 1 (Voriconazole (1R)-(−)-10-camphorsulfonate, 41.49 g wet, 40.36 g dry estimated, 0.069 mol) was suspended in ethyl acetate (121 ml) and aqueous saturated sodium bicarbonate solution (97 ml) was added slowly. The mixture was stirred for 10 minutes, the phases allowed to settle and the organic layer separated. The aqueous layer was re-extracted with ethyl acetate (91 ml). The combined organic layers were washed with deionised water (12 ml), filtered and concentrated under vacuum until a white doughy residue was obtained. Isopropanol (24 ml) was added and concentrated again under vacuum until a white doughy residue was obtained. Isopropanol (54.5 ml) was added and the suspension was heated until complete solution (60-65° C.). The solution was cooled down to 0-2° C. and stirred for at least 1 hour. The suspension formed was filtered, the cake was washed with cold isopropanol (6.1 ml). A white crystalline solid was obtained after drying at 55-60° C. under vacuum until constant weight: 19.75 g (81.43% yield).

Workup

  1. customthe organic layer separated
  2. extractionThe aqueous layer was re-extracted with ethyl acetate (91 ml)
  3. washThe combined organic layers were washed with deionised water (12 ml)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum until a white doughy residue
  6. customwas obtained
  7. concentrationconcentrated again under vacuum until a white doughy residue
  8. customwas obtained
  9. temperatureThe solution was cooled down to 0-2° C.
  10. stirringstirred for at least 1 hour
  11. customThe suspension formed
  12. filtrationwas filtered
  13. washthe cake was washed with cold isopropanol (6.1 ml)
  14. customA white crystalline solid was obtained
  15. customafter drying at 55-60° C. under vacuum until constant weight

Sources & evidence

ORD record
ord-df7156f487a44f2482806d22a2ac87ed
Source dataset
uspto-grants-2012_03
Patent number
US08143397B2

Reaction notes

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