Isopropanol → Nilvadipine

HRID 256601

반응식

HRID 256601 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

HCID 4494Nilvadipine수율 95.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-77bfd4d9bb8e4b79a65d1edd92bfbd1b
출처 데이터셋
uspto-grants-1993_11
특허 번호
US05258393

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