Hydrochloric Acid → HCID 66650706, compound

HRID 417984Notes

Reaction equation

HRID 417984 reaction equation
[ClH:1].Cl.Cl.[C:4]1([N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[O:17])[CH2:12][CH2:11]2)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.I[CH2:28][CH3:29].CCN(C(C)C)C(C)C.Cl>CN(C=O)C.C(Cl)Cl.CCOCC>[ClH:1].[ClH:1].[ClH:1].[C:4]1([N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][N:24]([CH2:28][CH3:29])[CH2:23][CH2:22]3)=[O:17])[CH2:12][CH2:11]2)[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6340IodoethaneHCID 81531DiisopropylethylamineHCID 66650707HCID 66650707, compound

Product 1

HCID 66650706HCID 66650706, compoundYield 142.5%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
170 °C

Procedure

2-(piperazin-1-yl)ethyl 4-phenylpiperazine-1-carboxylate (None HCl salt of Example 30; 291 mg, 0.91 mmol) was dissolved in DMF (2 mL). Iodoethane (74 μl, 2.31 mmol) and DIPEA (0.3 mL, 1.72 mmol) were added and the reaction mixture was heated at 170° C. for 15 minutes in a Biotage Initiator microwave at high absorption and then concentrated in vacuo. The residue was dissolved in 1 M aq Na2CO3 solution (25 mL) and extracted with DCM (3×25 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified normal phase column chromatography (eluting with DCM, followed by a 200:8:1 mixture of DCM:EtOH:NH3) followed by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-100%) to give a colourless oil. The oil was dissolved in DCM, treated with an excess of 2M HCl in Et2O and concentrated in vacuo to give 2-(4-ethylpiperazin-1-yl)ethyl 4-phenylpiperazine-1-carboxylate trihydrochloride (197 mg, 52%) as a white solid.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in 1 M aq Na2CO3 solution (25 mL)
  3. extractionextracted with DCM (3×25 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified normal phase column chromatography (
  7. washeluting with DCM
  8. additionfollowed by a 200:8:1 mixture of DCM
  9. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-100%)
  10. customto give a colourless oil
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b07dfae7b8a2452ea4f9f78f3a461258
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

Loading…