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 850000Notes

Reaction equation

HRID 850000 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-728ec0044ab94bbfb10d1d8a0e08d39f
Source dataset
uspto-grants-2000_01
Patent number
US06015819

Reaction notes

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