Water → Albaconazole

HRID 481023Notes

Reaction equation

HRID 481023 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]1([CH2:13][N:14]2[CH:18]=[N:17][CH:16]=[N:15]2)[C@H:11]([CH3:12])[O:10]1.[Cl:19][C:20]1[CH:29]=[C:28]2[C:23]([C:24](=[O:30])[NH:25][CH:26]=[N:27]2)=[CH:22][CH:21]=1.C([O-])([O-])=O.[K+].[K+].O>CN1CCCC1=O>[Cl:19][C:20]1[CH:29]=[C:28]2[C:23]([C:24](=[O:30])[N:25]([C@H:11]([CH3:12])[C@:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])([OH:10])[CH2:13][N:14]3[CH:18]=[N:17][CH:16]=[N:15]3)[CH:26]=[N:27]2)=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 101311911-((2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole, (2R-cis)-HCID 1354161757-Chloro-3H-quinazolin-4-one

Product 1

HCID 208952Albaconazole

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane (2.46 g, 9.8 mmol, obtained as described in Tasaka et al., Chem.Pharm.Bull. 1993, 41, 1035-1042) in N-methylpyrrolidone (10 mL), 7-chloro-3H-quinazolin-4-one (1.77 g, 9.8 mol) and K2CO3 (1.35 g, 9.8 mmol) were added. The resulting solution was heated at 80° C. for 3 days. The mixture was cooled to room temperature, water was then added and the pH was adjusted to 7. The mixture was extracted with ethyl acetate (4×). The combined organic extracts were washed with water (4×), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated to a reduced volume and was allowed to crystallize at 0° C. The resulting product was filtered, dried and dissolved in hot ethanol (10 mL/g). The insoluble material was filtered off, and the filtrate was then poured over cold water (120 mL/g of UR-9825) under stirring. The resulting precipitate was filtered and dried in vacuo (50° C.) to give the desired product as a white amorphous powder (3.1 g, 75%).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (4×)
  3. washThe combined organic extracts were washed with water (4×)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated to a reduced volume
  7. customto crystallize at 0° C
  8. filtrationThe resulting product was filtered
  9. customdried
  10. dissolutiondissolved in hot ethanol (10 mL/g)
  11. filtrationThe insoluble material was filtered off
  12. additionthe filtrate was then poured over cold water (120 mL/g of UR-9825)
  13. filtrationThe resulting precipitate was filtered
  14. customdried in vacuo (50° C.)

Sources & evidence

ORD record
ord-e72792f067ec4c7891c1a421dbc95877
Source dataset
uspto-grants-2003_11
Patent number
US06653475B2

Reaction notes

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