2-Bromoethyl methyl ether → [1-(2-Methoxyethyl)piperidin-4-yl]methyl 4-phenylpiperazine-1-carboxylate

HRID 417959Notes

Reaction equation

HRID 417959 reaction equation
[C:1]1([N:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[O:14])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:24][CH2:25][O:26][CH3:27].CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]1([N:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][CH2:16][CH:17]3[CH2:22][CH2:21][N:20]([CH2:24][CH2:25][O:26][CH3:27])[CH2:19][CH2:18]3)=[O:14])[CH2:11][CH2:12]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 809722-Bromoethyl methyl etherHCID 81531DiisopropylethylamineHCID 66650828(Piperidin-4-yl)methyl 4-phenylpiperazine-1-carboxylate

Product 1

HCID 42635434[1-(2-Methoxyethyl)piperidin-4-yl]methyl 4-phenylpiperazine-1-carboxylateYield 31.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

(Piperidin-4-yl)methyl 4-phenylpiperazine-1-carboxylate from the previous step (2.15 g, 7.10 mmol), 2-bromoethylmethylether (0.67 mL, 7.10 mmol) and DIPEA (1.36 mL, 7.81 mmol) were dissolved in DMF (30 mL) and stirred overnight at 70° C. and then concentrated in vacuo. The residue was dissolved in DCM (300 mL) and then washed sequentially with sat aq NaHCO3 solution (2×100 mL), brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 98:1:1 mixture of DCM:MeOH:DIPEA) followed by reverse phase chromatography (gradient eluting with MeOH in water, 0-100%) to give the title compound [1-(2-methoxyethyl)piperidin-4-yl]methyl 4-phenylpiperazine-1-carboxylate (0.798 g, 31.1% yield) as a viscous yellow oil.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in DCM (300 mL)
  3. washwashed sequentially with sat aq NaHCO3 solution (2×100 mL), brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by normal phase column chromatography (
  7. washeluting with DCM
  8. additionfollowed by a 98:1:1 mixture of DCM
  9. washMeOH:DIPEA) followed by reverse phase chromatography (gradient eluting with MeOH in water, 0-100%)

Sources & evidence

ORD record
ord-cc39110220164437a25e35aa94fd3d08
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

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