Morpholine → Methyl 2-methyl-2-(5-morpholino-3-nitropyridin-2-yl)propanoate

HRID 1618535Notes

Reaction equation

HRID 1618535 reaction equation
Br[C:2]1[CH:3]=[C:4]([N+:15]([O-:17])=[O:16])[C:5]([C:8]([CH3:14])([CH3:13])[C:9]([O:11][CH3:12])=[O:10])=[N:6][CH:7]=1.[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:13][C:8]([C:5]1[C:4]([N+:15]([O-:17])=[O:16])=[CH:3][C:2]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[CH:7][N:6]=1)([CH3:14])[C:9]([O:11][CH3:12])=[O:10]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 672852172-Pyridineacetic acid, 5-bromo-alpha,alpha-dimethyl-3-nitro-, methyl ester

Product 1

HCID 67285292Methyl 2-methyl-2-(5-morpholino-3-nitropyridin-2-yl)propanoate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A stirred mixture of methyl 2-(5-bromo-3-nitropyridin-2-yl)-2-methylpropanoate (1.2 g, 3.96 mmol), morpholine (0.34 mL, 3.96 mmol), Pd2dba3 (181 mg, 0.20 mmol), XPhos (189 mg, 0.40 mmol) and sodium tert-butoxide (1.1 g, 11.88 mmol) in toluene (30 mL) was heated at reflux for two h. After this time the reaction was cooled to rt and partitioned between EtOAc (300 mL) and water (100 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. Column chromatography gave methyl 2-methyl-2-(5-morpholino-3-nitropyridin-2-yl)propanoate as a yellow oil.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for two h
  3. custompartitioned between EtOAc (300 mL) and water (100 mL)
  4. dry with materialThe separated organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-ae509e17941d44298cc8f7580b9cc086
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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