4-Nitrobenzaldehyde → 3-Pyridinecarboxylic acid, 5-[[[3-(4,4-diphenyl-1-piperidinyl)propyl]amino]carbonyl]-1,4-dihydro-2,6-dimethyl-4-(4-nitrophenyl)-, methyl ester

HRID 1956402Notes

Reaction equation

HRID 1956402 reaction equation
[C:1]1([C:7]2([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][NH:16][C:17](=[O:22])[CH2:18][C:19]([CH3:21])=O)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:29]/[C:30](/[CH3:36])=[CH:31]\[C:32]([O:34][CH3:35])=[O:33].[N+:37]([C:40]1[CH:47]=[CH:46][C:43]([CH:44]=O)=[CH:42][CH:41]=1)([O-:39])=[O:38]>C(O)(C)C>[CH3:35][O:34][C:32]([C:31]1[CH:44]([C:43]2[CH:46]=[CH:47][C:40]([N+:37]([O-:39])=[O:38])=[CH:41][CH:42]=2)[C:18]([C:17]([NH:16][CH2:15][CH2:14][CH2:13][N:10]2[CH2:9][CH2:8][C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH2:12][CH2:11]2)=[O:22])=[C:19]([CH3:21])[NH:29][C:30]=1[CH3:36])=[O:33]

Participants

5

Reactant 3

HCID 5414-NitrobenzaldehydeHCID 643918Methyl 3-aminocrotonateHCID 10362296N-[3-(4,4-Diphenyl-piperidin-1-yl)-propyl]-3-oxo-butyramide

Product 1

HCID 98090073-Pyridinecarboxylic acid, 5-[[[3-(4,4-diphenyl-1-piperidinyl)propyl]amino]carbonyl]-1,4-dihydro-2,6-dimethyl-4-(4-nitrophenyl)-, methyl esterYield 25.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of acetoacetic acid N-[3-(4,4-diphenylpiperidin-1-yl)propyl]amide (365 mg, 0.964 mmol, 1.0 equiv), methyl 3-aminocrotonate (138 mg, 1.20 mmol, 1.2 equiv, Aldrich), and 4-nitrobenzaldehyde (181 mg, 1.20 mmol, 1.2 equiv, Aldrich) in isopropanol was refluxed under argon for 60 hours. The mixture was cooled to room temperature and concentrated, and the residue was diluted with CH2Cl2, washed with water, dried over MgSO4, and concentrated. The residue was purified by flash chromatography (SiO2, EtOAc, followed by EtOAc-MeOH, 19:1 and 9:1) to give 147.8 mg (25%) of yellow solid: 1H NMR (300 MHz, CDCl3) δ 1.55 (m, 2H), 2.14 (s, 3H), 2.15-2.50 (m, 10H), 2.32 (s, 3H), 3.20 (m, 1H), 3.37 (m, 1H), 3.54 (s, 3H), 5.00 (s, 3H), 5.48 (br s), 6.98 (br t, J=4.9 Hz, 1H), 7.14-7.30 (m, 10H), 7.39 (dm, J=8.7 Hz, 2H), 8.05 (dm, J=8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 18.74, 20.64, 25.61, 36.77, 40.20, 42.26, 45.03, 51.16, 51.61, 58.08, 100.65, 109.71, 124.35, 126.46, 127.61, 128.84, 129.06, 135.52, 146.96, 147.10, 154.55, 168.22, 168.70; IR (neat) 1680, 1610, 1515, 1340 cm-1 ; MS (FAB) m/e 609 (M+H)+.

Workup

  1. concentrationconcentrated
  2. additionthe residue was diluted with CH2Cl2
  3. washwashed with water
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (SiO2, EtOAc, followed by EtOAc-MeOH, 19:1 and 9:1)

Sources & evidence

ORD record
ord-08d77e651afa4677baa00566e14b6b36
Source dataset
uspto-grants-1998_07
Patent number
US05780485

Reaction notes

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