Methyl iodide → N1-(4-bromo-2-methoxyphenyl)-N1-methyl-3-phenylpropanamide

HRID 432314Notes

Reaction equation

HRID 432314 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:18])[CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:4]([O:19][CH3:20])[CH:3]=1.[H-].[Na+].[CH3:23]I>CN(C)C=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH3:23])[C:9](=[O:18])[CH2:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[C:4]([O:19][CH3:20])[CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydrideHCID 22346842N1-(4-bromo-2-methoxyphenyl)-3-phenylpropanamide

Product 1

HCID 22346968N1-(4-bromo-2-methoxyphenyl)-N1-methyl-3-phenylpropanamideYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N1-(4-bromo-2-methoxyphenyl)-3-phenylpropanamide (1.0 g, 3 mmol) in dimethylformamide (20 mL) at 0° C. was treated with pre-washed (3 times with heptane) sodium hydride (0.158 g, 6.6 mmol). The reaction mixture was stirred for 1 h at 0° C. Methyl iodide (0.511 g, 3.6 mmol) was added drop-wise, and the solution stirred for 15 min at 0° C. The ice bath was removed and the reaction mixture was stirred overnight at room temperature. The reaction did not go to completion over night; additional methyl iodide (0.511 g, 3.6 mmol) was added and the reaction mixture stirred over night. The reaction mixture was quenched with water (30 mL). Ethyl acetate was added, and the layers were partitioned. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting 3:1 heptane:ethyl acetate, and afforded 0.729 g (70%) of N1-(4-bromo-2-methoxyphenyl)-N1-methyl-3-phenylpropanamide. 1H NMR (DMSO-d6, 400 MHz) δ 7.330-7.326 (s, 1H), 7.235-7.178 (m, 2H), 7.161-7.116 (m, 3H), 7.058-7.040 (m, 2H), 3.811 (s, 3H), 3.002 (s, 3H), 2.753-2.708 (m, 2H), 2.282-2.204 (m, 1H), 2.138-2.061 (m, 1H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 7.366 min (96%).

Workup

  1. stirringthe solution stirred for 15 min at 0° C
  2. customThe ice bath was removed
  3. stirringthe reaction mixture was stirred overnight at room temperature
  4. waitThe reaction did not go to completion over night
  5. stirringthe reaction mixture stirred over night
  6. customThe reaction mixture was quenched with water (30 mL)
  7. additionEthyl acetate was added
  8. customthe layers were partitioned
  9. extractionThe aqueous layer was extracted with ethyl acetate
  10. washThe combined organic layers were washed with water and brine
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. customevaporated under reduced pressure
  14. customThe crude product was purified by flash chromatography on silica gel eluting 3:1 heptane

Sources & evidence

ORD record
ord-0fdb01d0b0164b07b9d996b101add7ab
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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