1-Chloromethylnaphthalene → Terbinafine Hydrochloride

HRID 1756314Notes

Reaction equation

HRID 1756314 reaction equation
[Cl:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1.Cl.[CH3:14][C:15]([CH3:24])([CH3:23])[C:16]#[C:17]/[CH:18]=[CH:19]/[CH2:20][NH:21][CH3:22].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CS(C)=O>[ClH:1].[CH3:14][C:15]([CH3:24])([CH3:23])[C:16]#[C:17]/[CH:18]=[CH:19]/[CH2:20][N:21]([CH3:22])[CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 68451-ChloromethylnaphthaleneHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 19917487(E)-N-methyl-6,6-dimethyl-2-hepten-4-ynylamine hydrochloride

Product 1

HCID 5282481Terbinafine HydrochlorideYield 90%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 1.77 g (10 mmol) of 1-chloromethylnaphthalene in 10 ml of dimethyl sulfoxide were added 1.88 g (10 mmol) of (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)methylamine hydrochloride and 1.66 g (12 mmol) of potassium carbonate under ice cooling. The mixture was stirred for 16 hours at room temperature, poured into 200 ml of ethyl acetate, washed with 100 ml×2 of water, a mixture of 80 ml of water and 10 ml of 2N hydrochloric acid, and 50 ml of saturated sodium chloride aqueous solution respectively, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to crystallize. The crystals were suspended in 10 ml of ethyl acetate, cooled, filtered and dried under reduced pressure to obtain 2.95 g (yield: 90%) of the above identified compound as off-white crystalline powder.

Workup

  1. washwashed with 100 ml×2 of water
  2. additiona mixture of 80 ml of water and 10 ml of 2N hydrochloric acid, and 50 ml of saturated sodium chloride aqueous solution respectively
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customto crystallize
  6. temperaturecooled
  7. filtrationfiltered
  8. customdried under reduced pressure
  9. customto obtain 2.95 g (yield: 90%) of the

Sources & evidence

ORD record
ord-60375dd4ac9a443a9e39b8ca6dc78dbe
Source dataset
uspto-grants-1995_08
Patent number
US05440049

Reaction notes

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