Morpholine → Methyl 3-methyl-4-morpholin-4-ylbenzoate

HRID 336254Notes

Reaction equation

HRID 336254 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH3:12].C([O-])([O-])=O.[Cs+].[Cs+].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:12][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=1[N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[C:6]([O:8][CH3:9])=[O:7]

Participants

7

Reactant 3

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 3294148Methyl 4-bromo-3-methylbenzoate

Product 1

HCID 67528858Methyl 3-methyl-4-morpholin-4-ylbenzoateYield 84%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 312751,4-DioxaneSolvent

Procedure

BINAP (0.67 g; 1.1 mmol; 0.05 eq.) and palladium acetate (0.24 g; 1.1 mmol; 0.05 eq.) were added to a suspension methyl 4-bromo-3-methylbenzoate (5 g; 21.8 mmol; 1 eq.), Cs2CO3 (10.65 g; 32.7 mmol; 1.5 eq.) and morpholine (2.3 g; 26 mmol; 1.2 eq.) in dioxane (100 mL) and the reaction mixture was refluxed for 15 hours. After filtration through a pad of CELITE, the solution was concentrated in vacuo and the residue purified by column chromatography (petroleum ether/ethyl acetate, 80/20) to afford the title compound (4.3 g, 84%) as a yellow solid.

Workup

  1. temperaturethe reaction mixture was refluxed for 15 hours
  2. filtrationAfter filtration through a pad of CELITE
  3. concentrationthe solution was concentrated in vacuo
  4. customthe residue purified by column chromatography (petroleum ether/ethyl acetate, 80/20)

Sources & evidence

ORD record
ord-734764d68c70478288b5d8255c75450c
Source dataset
uspto-grants-2014_11
Patent number
US08889668B2

Reaction notes

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