Morpholine → Methyl 3-methyl-5-(morpholin-4-yl)-1-benzofuran-2-carboxylate

HRID 2091391Notes

Reaction equation

HRID 2091391 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]([O:12][CH3:13])=[O:11])=[C:7]([CH3:14])[C:6]=2[CH:15]=1.[NH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>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]>[CH3:14][C:7]1[C:6]2[CH:15]=[C:2]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[CH:3]=[CH:4][C:5]=2[O:9][C:8]=1[C:10]([O:12][CH3:13])=[O:11]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 42967109Methyl 5-bromo-3-methylbenzofuran-2-carboxylate2×

Product 1

HCID 66778210Methyl 3-methyl-5-(morpholin-4-yl)-1-benzofuran-2-carboxylateYield 13%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a solution (100 mL) of methyl 5-bromo-3-methyl-1-benzofuran-2-carboxylate (5.4 g) synthesized in the above-mentioned (1) in toluene were added morpholine (5.2 mL), cesium carbonate (13.0 g), tris(dibenzylideneacetone)dipalladium (0) (0.92 g) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (1.1 g), and the mixture was heated under reflux under argon atmosphere for 20 hr. The reaction mixture was cooled to room temperature, and filtered through celite. Water was added to the residue, and the mixture was extracted with ethyl acetate. The extract was concentrated, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2, volume ratio) to give the title object compound (0.69 g, 13%) as a yellow oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux under argon atmosphere for 20 hr
  3. filtrationfiltered through celite
  4. additionWater was added to the residue
  5. extractionthe mixture was extracted with ethyl acetate
  6. concentrationThe extract was concentrated
  7. customthe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2, volume ratio)

Sources & evidence

ORD record
ord-7a68679e4664466f81799a6e84fb82e1
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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