Morpholine → rac-cis-N-((3-Methylpiperidin-2-yl)methyl)-5-(trifluoromethyl)pyridin-2-amine

HRID 60872Notes

Reaction equation

HRID 60872 reaction equation
[CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4](C(OCC=C)=O)[C@H:3]1[CH2:14][NH:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][N:17]=1.N1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1>[CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][NH:4][C@H:3]1[CH2:14][NH:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:23])[F:24])=[CH:18][N:17]=1

Participants

5

Reactant 2

HCID 8083MorpholineHCID 131737150HCID 131737150, compound

Product 1

HCID 131737152rac-cis-N-((3-Methylpiperidin-2-yl)methyl)-5-(trifluoromethyl)pyridin-2-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of rac-cis-allyl 3-methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)piperidine-1-carboxylate (1.18 g, 3.32 mmol), Pd(PPh3)4 (0.384 g, 0.003 mmol) and THF (20 mL) was added morpholine (3.0 mL, 33.2 mmol). The mixture was degassed for 5 min and stirred at rt. The reaction was monitored for disappearance of starting material by analytical reverse-phase HPLC. After ˜1 h, the reaction was concentrated in vacuo. The crude residue was taken up in EtOAc, and washed with sat aqueous NaHCO3, brine, dried (MgSO4), and concentrated and the resulting crude residue was purified by silica gel chromatography (0˜100% DCM/EtOAc) to afford the title compound ESI-MS (m/z): 472, [M+1]+.

Workup

  1. customThe mixture was degassed for 5 min
  2. concentrationthe reaction was concentrated in vacuo
  3. washwashed
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customthe resulting crude residue was purified by silica gel chromatography (0˜100% DCM/EtOAc)

Sources & evidence

ORD record
ord-6983e331d86645dabf69dc609d813da9
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

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