Potassium Hydroxide → (+)-1-(2-Methoxyethoxymethyl)-2,6-dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-carboxy-1,4-dihydropyridine

HRID 34401Notes

Reaction equation

HRID 34401 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:12]([CH3:13])=[C:11]([C:14]([O:16][CH3:17])=[O:15])[CH:10]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([N+:24]([O-:26])=[O:25])[CH:19]=2)[C:9]([C:27]([O:29]C)=[O:28])=[C:8]1[CH3:31].[OH-].[K+]>O.CO>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:8]([CH3:31])=[C:9]([C:27]([OH:29])=[O:28])[CH:10]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([N+:24]([O-:26])=[O:25])[CH:19]=2)[C:11]([C:14]([O:16][CH3:17])=[O:15])=[C:12]1[CH3:13]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 142087931-(2-Methoxyethoxy)methyl-2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine

Product 1

HCID 14208794(+)-1-(2-Methoxyethoxymethyl)-2,6-dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-carboxy-1,4-dihydropyridine

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

The N-protected diester is then mono-saponified, e.g., by heating with an alkali metal hydroxide or alkoxide (for example, NaOH, KOH, t-BuOK) or an alkali metal carbonate (for example K2CO3) in a water miscible solvent containing 10-45% water (preferably MeOH containing 15-40% water) at reflux temperature (or between 50° C. and reflux temperature for solvents other than MeOH) for 10 to 24 hours to yield an N-protected mono-ester. For example, 1-(2-methoxyethoxy)methyl-2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine in 20% H2O/MeOH is heated at reflux with aqueous KOH for 16 hours to yield racemic (RS)-1-(2-methoxyethoxy)methyl-2,6-dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-carboxy-1,4-dihydropyridine ((RS)-18). (Scheme VI, Step 2)

Sources & evidence

ORD record
ord-0b84e4ec59454e14a29d44a740e8310d
Source dataset
uspto-grants-1988_08
Patent number
US04761420

Reaction notes

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