Methyl iodide → 4-(2,6-Dichloro-4-methoxymethyl-phenoxy)-anisole

HRID 1168091Notes

Reaction equation

HRID 1168091 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:18][OH:19])[CH:5]=[C:6]([Cl:17])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1.[H-].[Na+].[H][H].[CH3:24]I>CN(C)C=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:18][O:19][CH3:24])[CH:5]=[C:6]([Cl:17])[C:7]=1[O:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 222856543,5-Dichloro-4-(4-methoxyphenoxy)benzyl AlcoholHCID 178418361HCID 178418361, compound

Product 1

HCID 222856594-(2,6-Dichloro-4-methoxymethyl-phenoxy)-anisoleYield 97.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of the title compound of Step A (400 mg, 1.34 mmol) in dry dimethylformamide (13 mL) at 0° C. under nitrogen was added NaH (60% dispersion in mineral oil, 134 mg, 3.3 mmol). After stirring for 30 minutes at 0° C. until hydrogen evolution ceased, methyl iodide (949 mg, 6.61 mmol) was added. The reaction mixture was warmed to room temperature and stirred for about 19 hours. The solution was poured into water (100 ml) and extracted with ethyl acetate (3×100 ml). The combined extracts were washed with 1M HCl (3×100 ml), brine (100 ml), dried, filtered, and concentrated. The crude product was purified by preparative TLC (30% hexane in dichloromethane) to afford the title compound (410 mg). NMR (400 MHz, CDCl3) δ7.36 (s, 2H), 6.75-6.83 (m, 4H), 4.40 (s, 2H), 3.75 (s, 3H), 3.43 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate (3×100 ml)
  2. washThe combined extracts were washed with 1M HCl (3×100 ml), brine (100 ml)
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by preparative TLC (30% hexane in dichloromethane)

Sources & evidence

ORD record
ord-567f5fcc4362481db6593d829cf33380
Source dataset
uspto-grants-2003_09
Patent number
US06620830B2

Reaction notes

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