Acetonitrile → Benzathine

HRID 625910Notes

Reaction equation

HRID 625910 reaction equation
[CH3:1][CH:2]([C:4]1[N:8]([CH2:9][CH2:10][C@@H:11]([OH:19])[CH2:12][C@@H:13]([OH:18])[CH2:14][C:15]([OH:17])=[O:16])[C:7]([C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)=[C:6]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:5]=1[C:33]([NH:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)=[O:34])[CH3:3].[C:42](#[N:44])[CH3:43]>O>[CH:4]1[CH:5]=[CH:6][C:43]([CH2:42][NH:44][CH2:10][CH2:9][NH:8][CH2:7][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:1][CH:2]=1.[CH3:3][CH:2]([C:4]1[N:8]([CH2:9][CH2:10][C@@H:11]([OH:19])[CH2:12][C@@H:13]([OH:18])[CH2:14][C:15]([OH:17])=[O:16])[C:7]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)=[C:6]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:5]=1[C:33]([NH:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:34])[CH3:1].[C:27]1([CH2:6][CH:7]([NH2:8])[CH2:20][NH2:44])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 2

HCID 6342Acetonitrile2×HCID 60823Atorvastatin2×

Product 3

HCID 8793BenzathineHCID 60823AtorvastatinHCID 4134343-Phenylpropane-1,2-diamine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The benzathine salt of atorvastatin (Form B) was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (1 g in 40 mL of ACN). A solution of N,N′-bis(phenylmethyl-1,2-ethanediamine (benzathine) was prepared by dissolving 220.64 mg (0.5 equivalents) in acetonitrile (80 mL) and water (20 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. After 2 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with acetonitrile (75 mL) to afford atorvastatin benzathine Form B. Note that this procedure is the same as above except that the sample was not oven dried.

Workup

  1. stirringAfter 2 days of stirring at ambient temperature
  2. customthe solids were isolated by vacuum filtration
  3. customfitted with a paper
  4. filtrationfilter (#2 Whatman)
  5. washThe solids were rinsed with acetonitrile (75 mL)

Sources & evidence

ORD record
ord-ab573950e6d44a62866ab63da35304f8
Source dataset
uspto-grants-2016_04
Patent number
US09309195B2

Reaction notes

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