Hydrochloric Acid → methyl N-(3,3-diphenylpropyl)-N-hydroxy-2-aminoethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate

HRID 1073363Notes

Reaction equation

HRID 1073363 reaction equation
C(N(CC)CC)C.[OH:8][NH:9][CH2:10][CH2:11][CH:12]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:25][C:26]1[NH:27][C:28]([CH3:51])=[C:29]([C:45]([O:47][CH2:48][CH2:49]Br)=[O:46])[CH:30]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([N+:42]([O-:44])=[O:43])[CH:37]=2)[C:31]=1[C:32]([O:34][CH3:35])=[O:33].Cl>CN(C)C=O.CC(C)=O.C(OCC)C.O>[CH3:25][C:26]1[NH:27][C:28]([CH3:51])=[C:29]([C:45]([O:47][CH2:48][CH2:49][N:9]([CH2:10][CH2:11][CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[OH:8])=[O:46])[CH:30]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([N+:42]([O-:44])=[O:43])[CH:37]=2)[C:31]=1[C:32]([O:34][CH3:35])=[O:33]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 13370972HCID 13370972, compoundHCID 22158922HCID 22158922, compound

Product 1

HCID 86741862methyl N-(3,3-diphenylpropyl)-N-hydroxy-2-aminoethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

3 ml of triethylamine were added to a solution of 2.40 g of N-hydroxy-3,3-diphenylpropylamine in 17 ml of dimethylformamide. 4.39 g of methyl 2-bromoethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate were added to the mixture. The mixture was then maintained in a nitrogen atmosphere and heated for 160 minutes at 105° C. After cooling, the mixture was poured into water and extracted with a diethyl ether: ethyl acetate mixture. The organic layer was washed many times with water and then dried. The solvent was evaporated off in vacuo. The oily residue obtained was purified first by chromatography on a silica gel column with ethyl acetate gradient in toluene and then on a silica gel column containing ammonia at 5.5% by weight with about 6N methanolic ammonia gradient in chloroform. The solid thus obtained was dissolved in a 2:1 by volume acetone: diethyl ether mixture and hydrogen chloride in diethyl ether was added. The hydrochloride hemihydrate of the title compound was filtered off, washed with isopropanol and dried at 100° C. and 0.5 mmHg for 1 hour. Yield 1.51 g, m.p. 100°-105° C.

Workup

  1. temperatureThe mixture was then maintained in a nitrogen atmosphere
  2. temperatureAfter cooling
  3. extractionextracted with a diethyl ether
  4. washThe organic layer was washed many times with water
  5. customdried
  6. customThe solvent was evaporated off in vacuo
  7. customThe oily residue obtained
  8. customwas purified first by chromatography on a silica gel column with ethyl acetate gradient in toluene
  9. additionon a silica gel column containing ammonia at 5.5% by weight with about 6N methanolic ammonia gradient in chloroform
  10. customThe solid thus obtained
  11. filtrationThe hydrochloride hemihydrate of the title compound was filtered off
  12. washwashed with isopropanol
  13. customdried at 100° C.

Sources & evidence

ORD record
ord-3c3ad699b73147c9b08fbac2f501bb1f
Source dataset
uspto-grants-1990_11
Patent number
US04968832

Reaction notes

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