Butylamine → Terbinafine Hydrochloride

HRID 484534

Reaction equation

HRID 484534 reaction equation
[Cl:1]/[CH:2]=[CH:3]/[CH2:4][N:5]([CH3:17])[CH2:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9][CH:8]=1.C(N)CCC.[C:23]([C:27]#[CH:28])([CH3:26])([CH3:25])[CH3:24]>[Cu]I.O1CCCC1>[ClH:1].[CH3:24][C:23]([CH3:26])([CH3:25])[C:27]#[C:28]/[CH:2]=[CH:3]/[CH2:4][N:5]([CH3:17])[CH2:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 3

HCID 8007ButylamineHCID 135123,3-Dimethyl-1-butyneHCID 9834733(E)-3-Chloro-N-methyl-N-(1-naphthylmethyl)-2-propen-1-amine

Product 1

HCID 5282481Terbinafine HydrochlorideYield 89%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To 33 ml of tetrahydrofuran were added 5.40 g (22 mmol) of (E)-N-(3-chloro-2-propenyl)-N-methyl-1-naphthalenemethanamine, 210 mg (1.1 mmol) of copper (I) iodide and 356 mg (0.31 mmol) of tetrakis (triphenylphosphine)palladium, and further, 4.35 ml (44 mmol) of n-butylamine and 2.83 ml (23.1 mmol) of tert-butylacetylene under ice cooling. The mixture was stirred for 17 hours at room temperature. The reaction mixture was concentrated and the residue was subjected to silica gel chromatography (n-hexane→n-hexane/ethyl acetate=9/1→4/1). The desired fractions were put together and concentrated under reduced pressure. The oily residue was dissolved in 6 ml of ethanol and 6 ml of 23% hydrogen chloride methanol solution was added thereto. The solvent and excess hydrogen chloride were distilled off. The resulting crystals were suspended in diisopropyl ether, filtered, washed with diisopropyl ether and dried to obtain 6.41 g (yield: 89%) of the above identified compound as white crystalline powder.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe oily residue was dissolved in 6 ml of ethanol
  4. addition6 ml of 23% hydrogen chloride methanol solution was added
  5. distillationThe solvent and excess hydrogen chloride were distilled off
  6. filtrationfiltered
  7. washwashed with diisopropyl ether
  8. customdried
  9. customto obtain 6.41 g (yield: 89%) of the

Sources & evidence

ORD record
ord-3a6398c8ca134856b3af144348d8ccab
Source dataset
uspto-grants-1993_07
Patent number
US05231183

Linked notes

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