Diisopropylethylamine → 1-[2-(Isochroman-1-yl)ethyl]-4-(2-methylphenyl)piperazine dihydrochloride

HRID 1417795

Reaction equation

HRID 1417795 reaction equation
[Cl:1][CH2:2]CC1C2C(=CC=CC=2)CCO1.O.[ClH:15].Cl.[CH:17]1([CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][N:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3OC)[CH2:31][CH2:30]2)[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][CH2:19][O:18]1.C(N(C(C)C)CC)(C)C>C(O)CO>[ClH:1].[ClH:15].[CH:17]1([CH2:27][CH2:28][N:29]2[CH2:30][CH2:31][N:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[CH3:2])[CH2:33][CH2:34]2)[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][CH2:19][O:18]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 10607966HCID 10607966, compoundHCID 232889511-[2-(Isochroman-1-yl)ethyl]-4-(2-methoxyphenyl)piperazine dihydrochloride monohydrate

Product 1

HCID 232887581-[2-(Isochroman-1-yl)ethyl]-4-(2-methylphenyl)piperazine dihydrochloride

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Procedure

A mixture of 1-(2-chloroethyl)isochroman (LXIV, PREPARATION 2, 0.2466 g, 1.25 mmol), 1-(2-methylphenyl)piperazine dihydrochloride (XI, 0.5327 g, 2.14 mmol), diisopropylethylamine (0.98 ml, 5.63 mmol) and ethylene glycol (2.5 ml) is stirred under nitrogen at 100° for 3 days. The reaction mixture is cooled and partitioned between aqueous sodium bicarbonate and ethyl acetate. The combined organic phase is washed with saline, dried over magnesium sulfate and concentrated. The residue is chromatographed on silica gel eluting with methanol/dichloromethane (2/98). The appropriate fractions are pooled and concentrated to give the free base of the title compound. The dihydrochloride salt is formed using hydrochloric acid/methanol to give the title compound, mp 207.5°-210.5°; MS (m/z) 336; IR (mineral oil) 770, 2406, 2435, 2992, 2364 and 1489 cm-1.

Workup

  1. temperatureThe reaction mixture is cooled
  2. custompartitioned between aqueous sodium bicarbonate and ethyl acetate
  3. washThe combined organic phase is washed with saline
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue is chromatographed on silica gel eluting with methanol/dichloromethane (2/98)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-dffdeaf7ad5842958956bc5adc5432f8
Source dataset
uspto-grants-1999_03
Patent number
US05877317

Linked notes

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