3-Nitrobenzaldehyde → Nicardipine Impurity 19

HRID 568934

반응식

HRID 568934 반응식
[C:1]([O-:7])(=[O:6])[CH2:2][C:3]([CH3:5])=O.[N+:8]([C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=1)[CH:14]=O)([O-:10])=[O:9].C(O)(=O)C.N1CCCCC1.[NH2:29]/[C:30](/[CH3:39])=[CH:31]\[C:32]([O:34][CH2:35][CH2:36][C:37]#[N:38])=[O:33]>C1C=CC=CC=1.C(O)(C)C>[C:37]([CH2:36][CH2:35][O:34][C:32]([C:31]1[CH:14]([C:13]2[CH:16]=[CH:17][CH:18]=[C:11]([N+:8]([O-:10])=[O:9])[CH:12]=2)[C:2]([C:1]([OH:7])=[O:6])=[C:3]([CH3:5])[NH:29][C:30]=1[CH3:39])=[O:33])#[N:38]

참가 물질

7

반응물 4

HCID 74493-NitrobenzaldehydeHCID 6971017AcetoacetateHCID 9793820Piperidine, acetateHCID 136714102-Cyanoethyl 3-aminocrotonate

생성물 1

HCID 10429284Nicardipine Impurity 19수율 84.1%

시약·촉매·용매 2

HCID 241Benzene용매HCID 3776Isopropanol용매

실험 절차

20.5 g of 2-nitratopropyl acetoacetate, 15.1 g of 3-nitrobenzaldehyde and 1.5 g of piperidine acetate in 74 ml of benzene were heated at reflux under azeotropic dehydration conditions for 2 hours. The reaction solution was washed, in turn, with 25 ml of water, 25 ml of an aqueous 1N sodium bisulfite solution and 25 ml of water and dried over anhydrous sodium sulfate, and the benzene was evaporated under reduced pressure. To the residue thus obtained was added 15.4 g of 2-cyanoethyl 3-aminocrotonate, and the mixture was taken up in 44 ml of isopropyl alcohol, heated at reflux for 3 hours and cooled on ice. The crystals which precipitated were collected by filtration, dried, applied to a silica gel column chromatography [eluent: a mixture of hexane and ethyl acetate (1:1)] and recrystallized from isopropyl alcohol to give 31.2 g of 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-(2-cyanoethyl) ester 5-(2-nitratopropyl) ester.

후처리

  1. temperatureat reflux under azeotropic dehydration conditions for 2 hours
  2. washThe reaction solution was washed, in turn, with 25 ml of water, 25 ml of an aqueous 1N sodium bisulfite solution and 25 ml of water
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe benzene was evaporated under reduced pressure
  5. customTo the residue thus obtained
  6. temperatureheated
  7. temperatureat reflux for 3 hours
  8. temperaturecooled on ice
  9. customThe crystals which precipitated
  10. filtrationwere collected by filtration
  11. customdried
  12. additiona mixture of hexane and ethyl acetate (1:1)] and
  13. customrecrystallized from isopropyl alcohol

출처 및 근거

ORD 기록
ord-285af784a44a4ec1b97c1dc94e014538
출처 데이터셋
uspto-grants-1988_03
특허 번호
US04730052

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