Morpholine → 4-[6-(Piperidin-1-ylcarbonyl)pyridin-3-yl]morpholine

HRID 2404262Notes

Reaction equation

HRID 2404262 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]([C:8]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[O:9])=[N:6][CH:7]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[N:10]1([C:8]([C:5]2[N:6]=[CH:7][C:2]([N:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[CH:3][CH:4]=2)=[O:9])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 67151381HCID 67151381, compound

Product 1

HCID 671512274-[6-(Piperidin-1-ylcarbonyl)pyridin-3-yl]morpholineYield 37%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-iodo-2-(piperidin-1-ylcarbonyl)pyridine (71 g, 0.23 mol), palladium (II) acetate (1.03 g, 46 mmol), 2-(di-tert-butylphosphino)biphenyl (2.76 g, 92 mmol), morpholine (23.7 g, 0.28 mol), and sodium tert-butoxide (27.8 g, 0.28 mol) in toluene (400 mL) was stirred under argon at 95 C for 2 hours. The product was isolated by chromatography (silica gel, ethyl acetate) and recrystallized from ethanol to give 4-[6-(piperidin-1-ylcarbonyl)pyridin-3-yl]morpholine (yield 37%, 22 g).

Workup

  1. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-745b664c4d2a47e2a7835391921a68da
Source dataset
uspto-grants-2014_08
Patent number
US08802690B2

Reaction notes

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