3-Nitrobenzaldehyde → 2-(N-benzyl-N-methylamino)-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-diisopropoxyphosphinyl-1,4-dihydropyridine-3-carboxylate

HRID 485077Notes

Reaction equation

HRID 485077 reaction equation
[CH2:1]([P:5](=[O:14])([O:10][CH:11]([CH3:13])[CH3:12])[O:6][CH:7]([CH3:9])[CH3:8])[C:2]([CH3:4])=O.[N+:15]([C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=1)[CH:21]=O)([O-:17])=[O:16].C(O)(=O)C.N1CCCCC1.[NH2:36]/[C:37](/[CH3:53])=[CH:38]\[C:39]([O:41][CH2:42][CH2:43][N:44]([CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[CH3:45])=[O:40]>C(O)(C)C>[CH3:53][C:37]1[NH:36][C:2]([CH3:4])=[C:1]([P:5]([O:10][CH:11]([CH3:13])[CH3:12])([O:6][CH:7]([CH3:9])[CH3:8])=[O:14])[CH:21]([C:20]2[CH:23]=[CH:24][CH:25]=[C:18]([N+:15]([O-:17])=[O:16])[CH:19]=2)[C:38]=1[C:39]([O:41][CH2:42][CH2:43][N:44]([CH2:46][C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1)[CH3:45])=[O:40]

Participants

6

Reactant 4

HCID 74493-NitrobenzaldehydeHCID 9793820Piperidine, acetateHCID 125291882-(N-Benzyl-N-methylamino)ethyl 3-amino-2-butenoateHCID 12616936Diisopropyl acetonylphosphonate

Product 1

HCID 133636742-(N-benzyl-N-methylamino)-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-diisopropoxyphosphinyl-1,4-dihydropyridine-3-carboxylateYield 52%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 2.22 grams of diisopropyl acetonylphosphonate and 1.51 grams of m-nitrobenzaldehyde was added to 10 ml of isopropanol, 300 mg of piperidine acetate was added thereto, and the mixture was heated to reflux for three hours with stirring. To this was added 2.48 grams of 2-(N-benzyl-N-methylamino)-ethyl 3-aminocrotonate and the mixture was heated to reflux for another five hours with stirring. The reaction mixture was concentrated, the residue was dissolved in ethyl acetate, the solution was washed with 1N aqueous solution of sodium hydroxide, aqueous solution of sodium bisulfite, and water, successively, then separated after addition of 1N hydrochloric acid solution, to the lower layer was added chloform followed by separation, the chloroform layer was washed with 5% aqueous solution of potassium carbonate and then with water, and dried. Chloroform was evaporated therefrom in vacuo, the residue was purified by subjecting to silica gel column chromatography (100 grams of silica gel used; eluting solution: ethyl acetate) and the resulting crystals were recrystallized from ethyl acetate to afford 3.04 grams of 2-(N-benzyl-N-methylamino)-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-diisopropoxyphosphinyl-1,4-dihydropyridine-3-carboxylate, melting point 113°-15° C., melting point of the hydrochloride 119° C.

Workup

  1. additionwas added
  2. temperaturethe mixture was heated
  3. temperatureto reflux for three hours
  4. temperaturethe mixture was heated
  5. temperatureto reflux for another five hours
  6. stirringwith stirring
  7. concentrationThe reaction mixture was concentrated
  8. dissolutionthe residue was dissolved in ethyl acetate
  9. washthe solution was washed with 1N aqueous solution of sodium hydroxide, aqueous solution of sodium bisulfite, and water
  10. customsuccessively, then separated
  11. additionafter addition of 1N hydrochloric acid solution
  12. additionto the lower layer was added chloform
  13. customfollowed by separation
  14. washthe chloroform layer was washed with 5% aqueous solution of potassium carbonate
  15. dry with materialwith water, and dried
  16. customChloroform was evaporated
  17. customin vacuo, the residue was purified
  18. customthe resulting crystals were recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-d1aa78d63ed94e58a3db02795f8f3850
Source dataset
uspto-grants-1985_08
Patent number
US04535073

Reaction notes

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