Sodium Iodide → N-(3-{1-[4-(3,4-Dimethylphenyl)-4-Oxobutyl]-4-Piperidinyl}Phenyl)-2-Methylpropanamide

HRID 2087157Notes

Reaction equation

HRID 2087157 reaction equation
[CH3:1][CH:2]([CH3:18])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:7]=1)=[O:4].Cl[CH2:20][CH2:21][CH2:22][C:23]([C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[C:27]([CH3:32])[CH:26]=1)=[O:24].C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>CN(C=O)C>[CH3:32][C:27]1[CH:26]=[C:25]([C:23](=[O:24])[CH2:22][CH2:21][CH2:20][N:15]2[CH2:16][CH2:17][CH:12]([C:8]3[CH:7]=[C:6]([NH:5][C:3](=[O:4])[CH:2]([CH3:18])[CH3:1])[CH:11]=[CH:10][CH:9]=3)[CH2:13][CH2:14]2)[CH:30]=[CH:29][C:28]=1[CH3:31]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 987424-Chloro-3',4'-dimethylbutyrophenoneHCID 167572552-methyl-N-[3-(4-piperidyl)phenyl]propanamide

Product 1

HCID 10112881N-(3-{1-[4-(3,4-Dimethylphenyl)-4-Oxobutyl]-4-Piperidinyl}Phenyl)-2-MethylpropanamideYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 0.0500 g (0.200 mmol) of 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide, 0.100 g (0.480 mmol) of 4-chloro-3′,4′-dimethylbutyrophenone, 0.080 g (0.600 mmol) of K2CO3 and 0.090 g (0.600 mmol) of NaI in 5 mL of DMF was heated at reflux temperature for 18 hours. The reaction mixture was filtered, the filtrate was poured into 5 mL of water and washed with 3×5 mL of ethyl acetate. The combined organic extracts were dried (MgSO4), concentrated in vacuo and purified by preparative TLC (silica; 9.5:0.5, dichloromethane:methanol+1% isopropyl amine) to afford 0.067 g (80.0% yield) of the desired product: 1H NMR (400 MHz, CDCl3) δ 7.72 (d, 1H, J=8.0 Hz), 7.44 (s, 1H), 7.38 (d, 1H, J=8.0 Hz), 7.23-7.20 (m, 2H), 7.16 (s, 1H), 6.95 (d, 1H, J=6.8 Hz), 3.13-3.11 (m, 2H), 3.02 (t, 2H, J=7.0 Hz), 2.56-2.40 (m, 4H), 2.32 (s, 6H), 2.17-2.15 (m, 2H), 2.04-1.78 (m, 6H), 1.25 (d, 6H, J=6.8 Hz); ESMS m/e 421.3 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 18 hours
  3. filtrationThe reaction mixture was filtered
  4. additionthe filtrate was poured into 5 mL of water
  5. washwashed with 3×5 mL of ethyl acetate
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. custompurified by preparative TLC (silica; 9.5:0.5, dichloromethane:methanol+1% isopropyl amine)

Sources & evidence

ORD record
ord-8b3898122f95492099a9d4a96d439043
Source dataset
uspto-grants-2004_04
Patent number
US06727264B1

Reaction notes

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