Acetyl chloride → Mexiletine acetate

HRID 2294273Notes

Reaction equation

HRID 2294273 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[CH3:5][C:6]1[C:11]([O:12][CH2:13][CH:14]([NH2:16])[CH3:15])=[C:10]([CH3:17])[CH:9]=[CH:8][CH:7]=1.Cl.C(OCC)(=O)C.[OH-].[Na+]>O>[CH3:5][C:6]1[CH:7]=[CH:8][CH:9]=[C:10]([CH3:17])[C:11]=1[O:12][CH2:13][CH:14]([NH:16][C:1](=[O:3])[CH3:2])[CH3:15]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 214671-Methyl-2-(2,6-xylyloxy)ethylammonium chloride

Product 1

HCID 567741Mexiletine acetateYield 96%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
17.5 °C

Procedure

Acetyl chloride (99 ml, 1.39 mol, 1.5 eq) was added to a stirred suspension of mexiletine hydrochloride (200 g, 0.927 mol), ethyl acetate (750 ml), and 5N sodium hydroxide (750 ml) over a period of 35 minutes while keeping the temperature at ≤10° C. After the addition was complete, the reaction was allowed to stir for 45 minutes at 15-20° C. The mixture was then added to water (1 1) and the ethyl acetate layer separated. The aqueous layer was washed with ethyl acetate (2×300 ml) and the combined ethyl acetate layers were washed with saturated aqueous sodium bicarbonate until the washings were no longer acidic. The ethyl acetate solution was then washed with brine, dried over MgSO4, and concentrated to give N-[2-(2,6-dimethylphenoxy)-1-methylethyl]-acetamide (197 g, 96% yield, mp 85-85.8° C.).

Workup

  1. customat ≤10° C
  2. additionAfter the addition
  3. customthe ethyl acetate layer separated
  4. washThe aqueous layer was washed with ethyl acetate (2×300 ml)
  5. washthe combined ethyl acetate layers were washed with saturated aqueous sodium bicarbonate until the washings
  6. washThe ethyl acetate solution was then washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-0e608c4da7884a72993cc39fbe240047
Source dataset
uspto-grants-1997_11
Patent number
US05688830

Reaction notes

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