Sodium Hydroxide → (+)-Amlodipine

HRID 2244768Notes

Reaction equation

HRID 2244768 reaction equation
[OH-].[Na+].[CH3:3][CH2:4][O:5][C:6]([C:8]1[C@H:13]([C:14]2[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:12]([C:21]([O:23][CH3:24])=[O:22])=[C:11]([CH3:25])[NH:10][C:9]=1[CH2:26][O:27][CH2:28][CH2:29][NH2:30])=[O:7].C([C@H]([C@@H](C([O-])=O)O)O)([O-])=O>ClCCl>[CH3:3][CH2:4][O:5][C:6]([C:8]1[C@H:13]([C:14]2[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:12]([C:21]([O:23][CH3:24])=[O:22])=[C:11]([CH3:25])[NH:10][C:9]=1[CH2:26][O:27][CH2:28][CH2:29][NH2:30])=[O:7]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 131727984(R)-(+)-amlodipine D-(-)-tartrate

Product 1

HCID 9801597(+)-AmlodipineYield 98.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

20 ml of dichloromethane and 10 ml of 2N aqueous NaOH were added into 1.8 g of (R)-(+)-amlodipine-D-(−)-tartrate, then reacted for 30 minutes under stirring. The solution was kept standing until organic phase is separated out. The organic phase was dried by adding anhydrous sodium carbonate and then filtered. The filter cake was washed with small amount of dichloromethane. The filter solution together with the washed dichloromethane were concentrated under reduced pressure, then crystallized under stirring and filtered following by adding n-hexane. The crystal thus obtained was dried under vacuum overnight to give 1.3 g of (R)-(+)-amlodipine Enantiomeric excess (ee) determinated by chiral column HPLC is 98.8% and yield is 52%.

Workup

  1. customreacted for 30 minutes
  2. customis separated out
  3. customThe organic phase was dried
  4. additionby adding anhydrous sodium carbonate
  5. filtrationfiltered
  6. washThe filter cake was washed with small amount of dichloromethane
  7. concentrationThe filter solution together with the washed dichloromethane were concentrated under reduced pressure
  8. customcrystallized
  9. stirringunder stirring
  10. filtrationfiltered
  11. additionby adding n-hexane
  12. customThe crystal thus obtained
  13. customwas dried under vacuum overnight

Sources & evidence

ORD record
ord-0df2a054d5b54c8a8067c805ab2ec2be
Source dataset
uspto-grants-2010_03
Patent number
US07678921B2

Reaction notes

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