Citric Acid → Sildenafil Citrate

HRID 1435820Notes

Reaction equation

HRID 1435820 reaction equation
[CH3:1][CH2:2][CH2:3][C:4]1[C:5]2[N:14]=[C:13]([C:15]3[CH:16]=[C:17]([S:24]([N:27]4[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]4)(=[O:26])=[O:25])[CH:18]=[CH:19][C:20]=3[O:21][CH2:22][CH3:23])[NH:12][C:10](=[O:11])[C:6]=2[N:7]([CH3:9])[N:8]=1.[C:34]([OH:46])(=[O:45])[CH2:35][C:36]([CH2:41][C:42]([OH:44])=[O:43])([C:38]([OH:40])=[O:39])[OH:37]>CC(C)=O>[CH3:1][CH2:2][CH2:3][C:4]1[C:5]2[N:14]=[C:13]([C:15]3[CH:16]=[C:17]([S:24]([N:27]4[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]4)(=[O:25])=[O:26])[CH:18]=[CH:19][C:20]=3[O:21][CH2:22][CH3:23])[NH:12][C:10](=[O:11])[C:6]=2[N:7]([CH3:9])[N:8]=1.[CH2:41]([C:36]([OH:37])([C:38]([OH:40])=[O:39])[CH2:35][C:34]([OH:46])=[O:45])[C:42]([OH:44])=[O:43]

Participants

4

Reactant 2

HCID 311Citric AcidHCID 135398744Sildenafil

Product 1

HCID 135413523Sildenafil CitrateYield 95.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

In a 3-necked flask sildenafil (5 g, 10 mmol) was dissolved in acetone (40 ml) at 50° C. In a separate container, citric acid (2 g, 10 mmol) was dissolved in acetone (15 ml). Both solutions were filtered. The citric acid solution was added dropwise to the sildenafil solution and a white precipitate appeared immediately. Thereafter, the reaction mixture was heated and maintained at the solvent reflux temperature for 1 hour and subsequently allowed to cool over 3 hours to room temperature. The precipitate was collected by filtration and dried at 50° C. under 10 mm Hg to give sildenafil citrate in 95.5% yield.

Workup

  1. filtrationBoth solutions were filtered
  2. additionThe citric acid solution was added dropwise to the sildenafil solution
  3. temperatureThereafter, the reaction mixture was heated
  4. temperaturemaintained at the solvent
  5. temperaturereflux temperature for 1 hour
  6. temperatureto cool over 3 hours to room temperature
  7. filtrationThe precipitate was collected by filtration
  8. customdried at 50° C. under 10 mm Hg

Sources & evidence

ORD record
ord-977dec4acffa4ae69e061d7459fcb077
Source dataset
uspto-grants-2009_11
Patent number
US07618976B2

Reaction notes

Loading…