Methyl iodide → N-(3-{1-[4-(3,4-Dimethylphenyl)-4-oxobutyl)-4-piperidinyl}phenyl)-N,2-dimethylpropanamide

HRID 1832260Notes

Reaction equation

HRID 1832260 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:9](=[O:31])[CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=3)[CH2:15][CH2:14]2)[CH:5]=[CH:6][C:7]=1[CH3:8].CI.[CH3:34]C([O-])(C)C.[Na+].C1COCC1>O>[CH3:1][C:2]1[CH:3]=[C:4]([C:9](=[O:31])[CH2:10][CH2:11][CH2:12][N:13]2[CH2:14][CH2:15][CH:16]([C:19]3[CH:20]=[C:21]([N:25]([CH3:34])[C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=3)[CH2:17][CH2:18]2)[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 10112881N-(3-{1-[4-(3,4-Dimethylphenyl)-4-Oxobutyl]-4-Piperidinyl}Phenyl)-2-MethylpropanamideHCID 23676156Sodium t-butoxide

Product 1

HCID 22048884N-(3-{1-[4-(3,4-Dimethylphenyl)-4-oxobutyl)-4-piperidinyl}phenyl)-N,2-dimethylpropanamideYield 89.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of N-(3-{1-[4-(3,4-dimethylphenyl)-4-oxobutyl]-4-piperidinyl}phenyl)-2-methylpropanamide (15.0 mg, 0.0357 mmol), MeI (5.07 mg, 0.0357 mmol), NaOtBu (6.86 mg, 0.0714 mmol) and THF (1.00 mL) was stirred for 5 h at 25° C. The resulting crude mixture was diluted with water (10 mL), the aqueous layer was extracted with CH2Cl2 (3×20 mL). The combined organic layers were concentrated in vacuo and the residue was purified by preparative TLC using 4.0% of NH3 (2.0 M in methanol) in CH2Cl2 to afford the desired product N-(3-{1-[4-(3,4-dimethylphenyl)-4-oxobutyl]-4-piperidinyl}phenyl)-N,2-dimethylpropanamide (13.8 mg, 89.1%): 1H NMR (400 MHz, CDCl3) 7.76 (s, 1H), 7.72 (dd, 1H, J=1.8, 7.7 Hz), 7.33 (t, 1H, J=8.8 Hz), 7.22 (d, 1H, J=7.8 Hz), 7.18 (d, 1H, J=8.8 Hz), 7.01 (m, 2H), 3.24 (s, 3H), 3.10 (d, 1H, J=10.6 Hz), 3.00 (t, 1H, J=7.6 Hz), 2.49–2.44 (m, 4H), 2.33 (s, 6H), 2.112.10 (m, 2H), 1.99 (m, 1H), 1.79–1.77 (m, 4H), 1.26 (t, 2H, J=7.6 Hz), 1.02 (d, 6H, J=7.6 Hz); ESMS m/e: 435.2 (M+H)+.

Workup

  1. extractionthe aqueous layer was extracted with CH2Cl2 (3×20 mL)
  2. concentrationThe combined organic layers were concentrated in vacuo
  3. customthe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-354f3c00ab0f46aa9b4ceec45d422bbd
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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