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 394568Notes

Reaction equation

HRID 394568 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) δ1.55 (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) δ18.74, 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-6a0e4cb05f624703ab73a6b582a0b2d6
Source dataset
uspto-grants-2003_08
Patent number
US06602888B2

Reaction notes

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