Hydrochloric Acid → Morpholin-2-ylmethyl 4-phenylpiperazine-1-carboxylate dihydrochloride salt

HRID 2262489Notes

Reaction equation

HRID 2262489 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][O:15][C:16]([N:18]2[CH2:23][CH2:22][N:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:20][CH2:19]2)=[O:17])[CH2:9]1)=O)(C)(C)C.[ClH:30].CCOCC>CO>[ClH:30].[ClH:30].[C:24]1([N:21]2[CH2:22][CH2:23][N:18]([C:16]([O:15][CH2:14][CH:10]3[O:11][CH2:12][CH2:13][NH:8][CH2:9]3)=[O:17])[CH2:19][CH2:20]2)[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 669344832-(4-Phenylpiperazine-1-carbonyloxymethyl)-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 66934509Morpholin-2-ylmethyl 4-phenylpiperazine-1-carboxylate dihydrochloride saltYield 76%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-(4-phenylpiperazine-1-carbonyloxymethyl)-morpholine-4-carboxylic acid tert-butyl ester (6.67 g, 16.5 mmol) in MeOH (10 mL) was added 2M HCl in Et2O solution (16.5 mL, 32.9 mmol). The brown solution was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo. The residue purified by reverse phase column chromatography (LiChroprep RP-18, 40-63 μm, 460×26 mm (100 g), 30 mL/min, gradient 0% to 15% (over 75 min) MeOH in water with 0.1% TFA). The pure sample was stirred in a 4M aq HCl solution (20 mL) overnight before being concentrated in vacuo. The resulting yellow oil was washed with heptane, concentrated in vacuo and dried in a vacuum oven overnight to give the morpholin-2-ylmethyl 4-phenylpiperazine-1-carboxylate dihydrochloride salt (4.72 g, 76%) as a pale yellow solid.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe residue purified by reverse phase column chromatography (LiChroprep RP-18, 40-63 μm, 460×26 mm (100 g), 30 mL/min, gradient 0% to 15% (over 75 min) MeOH in water with 0.1% TFA)
  3. stirringThe pure sample was stirred in a 4M aq HCl solution (20 mL) overnight
  4. concentrationbefore being concentrated in vacuo
  5. washThe resulting yellow oil was washed with heptane
  6. concentrationconcentrated in vacuo
  7. customdried in a vacuum oven overnight

Sources & evidence

ORD record
ord-e2aad5cdccd1486d9aa601cbb14ad9c7
Source dataset
uspto-grants-2010_12
Patent number
US07851471B2

Reaction notes

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