Ethanol → Voriconazole

HRID 1051188Notes

Reaction equation

HRID 1051188 reaction equation
CC1(C)[C@@H]2CC[C@]1(CS([O:14][C@@:15]([C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=1[F:38])([C@H:22]([C:24]1[C:29]([F:30])=[CH:28][N:27]=[CH:26][N:25]=1)[CH3:23])[CH2:16][N:17]1[CH:21]=[N:20][CH:19]=[N:18]1)(=O)=O)C(=O)C2.CCO.C([O-])(=O)C.[Na+]>O>[F:38][C:32]1[CH:33]=[C:34]([F:37])[CH:35]=[CH:36][C:31]=1[C@:15]([OH:14])([C@H:22]([C:24]1[C:29]([F:30])=[CH:28][N:27]=[CH:26][N:25]=1)[CH3:23])[CH2:16][N:17]1[CH:21]=[N:20][CH:19]=[N:18]1

Participants

5

Reactant 3

HCID 702Ethanol2×HCID 517045Sodium AcetateHCID 118305435HCID 118305435, compound

Product 1

HCID 71616VoriconazoleYield 76%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent5×

Conditions

Temperature
32.5 °C

Procedure

To (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol ((1R,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonate (2.125 g) was added EtOH (3.8 mL) and water (3.8 mL). The slurry was heated to 32.5° C. which resulted in an almost colourless solution. This solution was then added in small aliquots (1 mL) to a chilled (0° C.) solution of sodium acetate (0.30 g) in water (4.1 mL) over 45 minutes. To the resulting slurry was then added a solution of EtOH (0.45 mL) and water (0.45 mL). The mixture was then allowed to stir at 2° C. for 30 minutes before water (4.5 mL) was gradually added over 20 minutes. The slurry was then stirred at 2° C. for 13.5 hours before the solids were isolated and reslurried at 0-5° C. twice in water (6.4 mL). The isolated solid was then dried at 45° C. for ˜48 hours at reduced pressure to give (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol as a white solid (0.969 g, 76% yield).

Workup

  1. customresulted in an almost colourless solution
  2. additionThis solution was then added in small aliquots (1 mL) to
  3. additionwas gradually added over 20 minutes
  4. customwere isolated
  5. customThe isolated solid was then dried at 45° C. for ˜48 hours at reduced pressure

Sources & evidence

ORD record
ord-a5cf01caccf9437a868b46a6b9ec9507
Source dataset
uspto-grants-2016_07
Patent number
US09388167B2

Reaction notes

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