Hydrochloric Acid → HCID 66934511, compound

HRID 2262486Notes

Reaction equation

HRID 2262486 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][C@H:9]1[CH2:15][O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:21][CH2:20]1)=[O:18])=O)(C)(C)C.[ClH:31].CCOCC>CO>[ClH:31].[ClH:31].[ClH:31].[C:25]1([N:22]2[CH2:23][CH2:24][N:19]([C:17]([O:16][CH2:15][C@@H:9]3[CH2:10][N:11]([CH3:14])[CH2:12][CH2:13][NH:8]3)=[O:18])[CH2:20][CH2:21]2)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 66934485HCID 66934485, compound

Product 1

HCID 66934511HCID 66934511, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-4-methyl-2-(4-phenyl-piperazine-1-carbonyloxymethyl)-piperazine-1-carboxylic acid tert-butyl ester (1.65 g, 3.9 mmol) in MeOH (10 mL) was added 2M HCl in Et2O solution (11.8 mL, 23.6 mmol). The reaction was stirred at room temperature for 3 days. The reaction mixture was concentrated in vacuo. The residue was 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 material was then purified further by reverse phase HPLC(YMC ODS-A 100×20 mm, 5 μm, 25 mL/min, gradient 50% to 100% (over 7 min) then 100% (3 min) MeOH in 10% MeOH/water). The pure product was stirred in 4M aq HCl solution (10 mL) for 4 hours before being concentrated in vacuo. The resulting oil was washed with heptane, concentrated in vacuo and then dried in a vacuum oven overnight to afford the [(2S)-4-methylpiperazin-2-yl]methyl 4-phenylpiperazine-1-carboxylate trihydrochloride salt (1.63 g, 96%) as a pale brown solid.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe residue was 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. customThe material was then purified further by reverse phase HPLC(YMC ODS-A 100×20 mm, 5 μm, 25 mL/min, gradient 50% to 100% (over 7 min)
  4. custom100% (3 min) MeOH in 10% MeOH/water
  5. stirringThe pure product was stirred in 4M aq HCl solution (10 mL) for 4 hours
  6. concentrationbefore being concentrated in vacuo
  7. washThe resulting oil was washed with heptane
  8. concentrationconcentrated in vacuo
  9. customdried in a vacuum oven overnight

Sources & evidence

ORD record
ord-3e0c284a770549b7a06f8abdba815340
Source dataset
uspto-grants-2010_12
Patent number
US07851471B2

Reaction notes

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