Methyl iodide → 2-(4-chloro-phenyl)-2-methoxy-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-acetamide

HRID 1841639Notes

Reaction equation

HRID 1841639 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:26])[C:9]([NH:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]#[CH:23])=[C:16]([O:24][CH3:25])[CH:15]=2)=[O:10])=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:30]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([O:26][CH3:30])[C:9]([NH:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]#[CH:23])=[C:16]([O:24][CH3:25])[CH:15]=2)=[O:10])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 11474256Cga-380778

Product 1

HCID 111883752-(4-chloro-phenyl)-2-methoxy-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-Chloro-phenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-acetamide (2.6 g, 7.0 mmol) is dissolved in N,N-dimethylformamide (30 ml). Sodium hydride (0.18 g, 7.5 mmol) is added in portions at +5° C. The mixture is stirred for 30 minutes at room temperature. Subsequently iodomethane (1.1 g, 7.5 mmol) is added dropwise and the resulting mixture is stirred for further 3 hours at room temperature. The reaction mixture is poured on ice/water (200 ml) and extracted with ethyl acetate (2×200 ml). The combined organic layer is washed with brine (200 ml) and dried over magnesium sulfate. After evaporation of the solvent, the residue is purified by chromatography (ethyl acetate/hexane) to yield 2-(4-chloro-phenyl)-2-methoxy-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-acetamide. 1H-NMR (300 MHz, CDCl3): 2.53 (t, 1H, C≡CH), 2.80 (t, 2H, CH2CH2), 3.34 (s, 3H, OCH3), 3.55 (t, 2H, CH2CH2), 3.84 (s, 3H, OCH3), 4.58 (s, 1H, CHOH), 4.79 (m, 2H, OCH2), 6.68-7.34 (m, 8H, CH arom., NH).

Workup

  1. stirringthe resulting mixture is stirred for further 3 hours at room temperature
  2. additionThe reaction mixture is poured on ice/water (200 ml)
  3. extractionextracted with ethyl acetate (2×200 ml)
  4. washThe combined organic layer is washed with brine (200 ml)
  5. dry with materialdried over magnesium sulfate
  6. customAfter evaporation of the solvent
  7. customthe residue is purified by chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-763e605affde4167876d10832a10edb0
Source dataset
uspto-grants-2004_01
Patent number
US06683211B1

Reaction notes

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