Citric Acid → Sildenafil Citrate

HRID 1435827Notes

Reaction equation

HRID 1435827 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 93.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

In a 0.5 L reactor equipped with mechanical stirrer, 370 ml acetone and 21.4 g wet sildenafil base were added. The mixture was heated to reflux. In a separate vessel, 8.95 g of citric acid was dissolved in 89.5 ml of acetone at room temperature. The solution was added dropwise. Upon completion of the addition, the reaction mixture was maintained at reflux for 1 hour, followed by 2 hours at room temperature. Sildenafil citrate precipitated during this period was filtered, and the cake was washed with acetone. 28.1 g wet sildenafil citrate was obtained and dried for 4 hours at 50° C. 25.5 g sildenafil citrate dry was obtained. (Yield of this step: 98.8%).

Workup

  1. customIn a 0.5 L reactor equipped with mechanical stirrer
  2. temperatureThe mixture was heated to reflux
  3. additionThe solution was added dropwise
  4. additionUpon completion of the addition
  5. temperaturethe reaction mixture was maintained
  6. temperatureat reflux for 1 hour
  7. customSildenafil citrate precipitated during this period
  8. filtrationwas filtered
  9. washthe cake was washed with acetone

Sources & evidence

ORD record
ord-723431ab4e1743f2ad1862b755ebe369
Source dataset
uspto-grants-2009_11
Patent number
US07618976B2

Reaction notes

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