Isopropanol → Nilvadipine

HRID 256601

反応式

HRID 256601 の反応式
[C:1]([C:4]1[CH:5]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([N+:23]([O-:25])=[O:24])[CH:18]=2)[C:6]([C:13]([O:15][CH3:16])=[O:14])=[C:7]([C:11]#[N:12])[NH:8][C:9]=1[CH3:10])([OH:3])=[O:2].P(Cl)(Cl)(Cl)(Cl)Cl.[CH:32](O)([CH3:34])[CH3:33].C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl>[C:11]([C:7]1[NH:8][C:9]([CH3:10])=[C:4]([C:1]([O:3][CH:32]([CH3:34])[CH3:33])=[O:2])[CH:5]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([N+:23]([O-:25])=[O:24])[CH:18]=2)[C:6]=1[C:13]([O:15][CH3:16])=[O:14])#[N:12]

参加物

6

反応物 4

HCID 3776IsopropanolHCID 10340Sodium CarbonateHCID 24819Phosphorus pentachlorideHCID 153887666-Cyano-5-methoxycarbonyl-2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

生成物 1

HCID 4494Nilvadipine収率 95.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

In methylene chloride (30 ml) is suspended methyl (+)-5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate (3.12 g) followed by addition of phosphorus pentachloride (2.46 g) with ice-cooling, and the mixture is stirred for 30 minutes. Then, a solution of isopropyl alcohol (1.4 g) in methylene chloride (10 ml) is added dropwise over a period of 10 minutes. The mixture is stirred for 20 minutes, at the end of which time 5% aqueous sodium carbonate solution (30 ml) is added and the mixture is stirred at ambient temperature for one hour. The organic layer is separated and the water layer is extracted with methylene chloride. The organic layers are combined, washed with aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The residue is purified by silica gel (75 g) column chromatography, elution being carried out with benzeneethyl acetate (10:1). The solvent is removed from the eluate under reduced pressure and the residue is crystallized from diisopropyl ether to provide 5-isopropyl 3-methyl (+)-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (3.34 g).

後処理

  1. temperaturecooling
  2. additionis added
  3. stirringthe mixture is stirred at ambient temperature for one hour
  4. customThe organic layer is separated
  5. extractionthe water layer is extracted with methylene chloride
  6. washwashed with aqueous sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationdistilled under reduced pressure
  9. customto remove the solvent
  10. customThe residue is purified by silica gel (75 g) column chromatography, elution
  11. customThe solvent is removed from the eluate under reduced pressure
  12. customthe residue is crystallized from diisopropyl ether

出典と根拠

ORDレコード
ord-77bfd4d9bb8e4b79a65d1edd92bfbd1b
出典データセット
uspto-grants-1993_11
特許番号
US05258393

関連ノート

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