2-(2-(2-Chloroethoxy)ethoxy)ethanol → 2-{2-[2-(2-Hydroxyethoxy)ethoxy]ethyl}-1H-isoindole-1,3(2H)-dione

HRID 1494583Notes

Reaction equation

HRID 1494583 reaction equation
NCCOCCOCC1NC(C)=C(C(OC)=O)C(C2C=CC=C(Cl)C=2Cl)C=1C(OCC)=O.Cl[CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][OH:42].[C:43]1(=[O:53])[NH:47][C:46](=[O:48])[C:45]2=[CH:49][CH:50]=[CH:51][CH:52]=[C:44]12.[K]>CN(C)C=O>[C:43]1(=[O:53])[N:47]([CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][OH:42])[C:46](=[O:48])[C:45]2=[CH:49][CH:50]=[CH:51][CH:52]=[C:44]12

Participants

5

Reactant 3

HCID 788712-(2-(2-Chloroethoxy)ethoxy)ethanolHCID 1315323-Ethyl 5-methyl 2-{[2-(2-aminoethoxy)ethoxy]methyl}-4-(2,3-dichlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylateHCID 24194345Phthalimide potassium salt

Product 1

HCID 111501572-{2-[2-(2-Hydroxyethoxy)ethoxy]ethyl}-1H-isoindole-1,3(2H)-dione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The subject of the present invention is also the process for preparing the (-)-2-{[2-(2-Aminoethoxy)ethoxy]methyl}-4-(2,3-dichlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine, wherein 2-[2-(2-chloroethoxy)ethoxy]ethanol is condensed with potassium phthalimide, in dimethylformamide in the heated state, to form 2-[2-(2-phtalimidoethoxy)ethoxy]ethanol the compound of the formula XIV: ##STR14## which is converted by means of Jones reagent to 2-[2-(2-phtalimidoethoxy)ethoxy]acetic acid, the compound of the formula XV: ##STR15## which is treated with carbonyldiimidazole and Meldrum's acid in the presence of pyridine in methylene chloride to obtain the compound of formula XVI: ##STR16## which is then reacted with (R)-2-phenyl-2-methoxyethanol, the compound of formula XVII: ##STR17## to obtain the β-keto ester of formula XVIII: ##STR18## which is condensed in the presence of ammonium formate in ethanol with a benzylidene compound of formula XIX: ##STR19## to obtain (4R,4'R/4S,4'R)-4-(2,3-dichlorophenyl)-5-methoxycarbonyl-3-(2-methoxy-2-phenylethoxycarbonyl)-6-methyl-2-{[2-(2-phthalimidoethoxy)ethoxy]methyl}-1,4-dihydropyridine, the compound of formula XX: ##STR20## and then: either: this compound is subjected to the action of aqueous sodium bicarbonate solution, in solution in acetonitrile, to obtain (4R,4'R/4S,4'R)-2-[{2-[2-(2-carboxyphenylcarboxamido)ethoxy]ethoxy}methyl]-4-(2,3-dichlorophenyl)-5-methoxycarbonyl-3-(2-methoxy-2-phenylethoxycarbonyl)-6-methyl-1,4-dihydropyridine, the compound of formula XXI: ##STR21## which is treated, after separation by HPLC, with a mixture of glyme and sodium ethylate to obtain a mixture containing (-)-2-[{2-[2-(2-carboxyphenylcarboxamido)ethoxy]ethoxy}methyl]-4-(2,3-dichlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine, the compound of formula XXII: ##STR22## and its homolog substituted at the 5-position with an ethoxycarbonyl radical,

Sources & evidence

ORD record
ord-1830f095b58a45ee96a5e85e0c6a3c04
Source dataset
uspto-grants-1991_06
Patent number
US05026863

Reaction notes

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