Cesium carbonate → 3-Methyl-4-(5-morpholin-4-ylmethyl-furan-2-yl)-benzoic acid methyl ester

HRID 606592Notes

Reaction equation

HRID 606592 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].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:37]1[O:41][C:40]([CH2:42][N:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)=[CH:39][CH:38]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CCOC(C)=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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.CN(C=O)C>[CH3:9][O:8][C:6](=[O:7])[C:5]1[CH:10]=[CH:11][C:2]([C:37]2[O:41][C:40]([CH2:42][N:43]3[CH2:44][CH2:45][O:46][CH2:47][CH2:48]3)=[CH:39][CH:38]=2)=[C:3]([CH3:12])[CH:4]=1

Participants

11

Reactant 5

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 3294148Methyl 4-bromo-3-methylbenzoateHCID 124786874-[(5-Bromofuran-2-yl)methyl]morpholine

Product 1

HCID 670475453-Methyl-4-(5-morpholin-4-ylmethyl-furan-2-yl)-benzoic acid methyl ester

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A three necked flask was charged with methyl 4-bromo-3-methylbenzoate (2.18 mmol), bis(pinacolato)diboron (2.29 mmol), palladium acetate (0.065 mmol), potassium acetate (6.54 mmol) and DMF (10 ml). The solution was degassed by bubbling through N2 gas for 30 mins and was then heated to 80° C. under N2 for 3 h. Reaction was then cooled to room temperature and 4-(5-Bromo-furan-2-ylmethyl)-morpholine (2.18 mmol), cesium carbonate (3.27 mmol) and Pd(PPh3)4 (0.065 mmol) added. The reaction was heated to 80° C. and stirred for a further 17 h. Mixture was then diluted with EtOAc and water and filtered through a celite pad to remove black particulates. The organic layer was separated, washed with brine and dried over Na2SO4 and concentrated in vacuo. Flash chromatography of the residue (silica, 10-99% EtOAc in hexane) gave 3-Methyl-4-(5-morpholin-4-ylmethyl-furan-2-yl)-benzoic acid methyl ester as a grey powdery solid: m/z in MS ES+=316 [M+H]+, 0.51 mmol, 23%.

Workup

  1. customThe solution was degassed
  2. customby bubbling through N2 gas for 30 mins
  3. customReaction
  4. temperaturewas then cooled to room temperature
  5. temperatureThe reaction was heated to 80° C.
  6. filtrationfiltered through a celite pad
  7. customto remove black particulates
  8. customThe organic layer was separated
  9. washwashed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e7821660fe3b4e0d87a0f6b0833f2330
Source dataset
uspto-grants-2011_03
Patent number
US07915300B2

Reaction notes

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