Hydrochloric Acid → 1-(4-Ethoxyphenyl)piperazine dihydrochloride

HRID 368839

Reaction equation

HRID 368839 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH3:22])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:23]>CO>[ClH:23].[ClH:23].[CH2:21]([O:20][C:17]1[CH:16]=[CH:15][C:14]([N:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[CH:19][CH:18]=1)[CH3:22]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 232888571-(Tert-butyloxycarbonyl)-4-(4-ethoxyphenyl)piperazine

Product 1

HCID 232887411-(4-Ethoxyphenyl)piperazine dihydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A mixture of 1-(tert-butyloxycarbonyl)-4-(4-hydroxyphenyl)piperazine (XXII, 0.602 g, 2.2 mmol) in dry THF (4 ml) is added to an ice-cooled slurry of sodium hydride (0.1013 g, 2.5 mmol--60% in oil) in THF (1 ml). DMF (15.3 ml) is added to solubilize the solids that had precipitated, after which ethyl iodide (0.34 ml, 4.3 mmol) is added. The ice/water bath is removed and the mixture stirred for five hr. Another portion of ethyl iodide (0.35 ml, 4.4 mmol) is added and the mixture is allowed ti stir over the weekend at 20-25°, at which time it is concentrated and the resulting solids are partitioned between ethyl acetate and aqueous saturated sodium bicarbonate. The combined organic phases are dried over magnesium sulfate, concentrated, and the residue chromatographed on silica gel eluting with methanol/dichloromethane (1/99) containing ammonium hydroxide (0.5%), followed by methanol/dichloromethane (2/98) containing ammonium hydroxide (0.5%). The appropriate fractions are pooled and concentrated to give 1-(tert-butyloxycarbonyl)-4-(4-ethoxyphenyl)piperazine (XXIII). 1-(Tert-butyloxycarbonyl)-4-(4-ethoxyphenyl)-piperazine (XXIII, 0.43 g) is dissolved in methanol and methanol saturated with hydrochloric acid gas is added. After stirring at 20-25° for 5 hours the slurry is concentrated and ether is added. The solids are collected, washed with ether, and dried to give 1-(4-ethoxyphenyl)piperazine dihydrochloride (XXIV), MS (m/z) 206; IR (mineral oil) 1253, 1511, 2542, 2432, 1475 and 2622 cm-1.

Workup

  1. concentrationis concentrated
  2. additionether is added
  3. customThe solids are collected
  4. washwashed with ether
  5. customdried

Sources & evidence

ORD record
ord-110624aae71c4888838075c955b533fa
Source dataset
uspto-grants-2000_10
Patent number
US06133446

Linked notes

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