4-Methylmorpholine → HCID 42635255, compound

HRID 417957Notes

Reaction equation

HRID 417957 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][OH:9])[CH2:4][CH2:3]1.CN1CC[O:14][CH2:13]C1.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=O.[CH3:30][O:31][C:32]1[CH:37]=[CH:36][C:35]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[CH:34][CH:33]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[CH3:30][O:31][C:32]1[CH:33]=[CH:34][C:35]([N:38]2[CH2:43][CH2:42][N:41]([C:13]([O:9][CH2:8][CH:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[O:14])[CH2:40][CH2:39]2)=[CH:36][CH:37]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 2697221-(4-Methoxyphenyl)piperazineHCID 2719711-Methyl-4-piperidinemethanol

Product 1

HCID 42635255HCID 42635255, compoundYield 10.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(1-Methylpiperidin-4-yl)methanol (1.00 g, 7.74 mmol) was dissolved in DCM (20 mL) and cooled to 0° C. NMM (0.94 mL, 8.51 mmol) and 4-nitrophenyl chloroformate (1.56 g, 7.74 mmol) were added. The reaction mixture was stirred at 0° C. for 20 minutes and then added to a solution of 4-(4-methoxyphenyl)piperazine (1.64 g, 8.51 mmol) and DIPEA (2.02 mL, 11.01 mmol) in DMF (30 mL). The reaction mixture was stirred at room temperature for 4 h and then concentrated in vacuo. The residue was dissolved in EtOAc (200 mL) and washed sequentially with 1 M aq NaOH solution (5×100 mL), brine (100 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-30%). The resulting residue was dissolved in DCM (70 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give (1-methylpiperidin-4-yl)methyl 4-(4-methoxyphenyl)piperazine-1-carboxylate (0.277 g, 10.3%) as an off-white solid.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 4 h
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in EtOAc (200 mL)
  4. washwashed sequentially with 1 M aq NaOH solution (5×100 mL), brine (100 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by reverse phase chromatography (gradient
  8. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
  9. dissolutionThe resulting residue was dissolved in DCM (70 mL)
  10. stirringstirred with solid K2CO3 for 20 minutes
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-66336688087146d39b7aa7874aa3281c
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

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