Morpholine → Methyl 2-methoxy-5-(morpholin-4-yl)benzoate

HRID 1012162Notes

Reaction equation

HRID 1012162 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8](I)[CH:7]=[CH:6][C:5]=1[O:11][CH3:12].[NH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.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]>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[CH:7]=[CH:6][C:5]=1[O:11][CH3:12]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 11011762Methyl 5-iodo-2-methoxybenzoate

Product 1

HCID 67105971Methyl 2-methoxy-5-(morpholin-4-yl)benzoateYield 39.8%

Reagents, catalysts & solvents 2

HCID 66545394HCID 66545394, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

5-Iodo-2-methoxy-benzoic acid methyl ester (500 mg, 1.7 mmol), morpholine (223 μl, 2.5 mmol), cesium carbonate (850 mg, 2.7 mmol), xantphos (60 mg, 0.1 mmol) and bis(dibenzylideneacetone)dipalladium (35 mg, 0.04 mmol) were suspended in dioxane (5 ml) and heated at 100° C. for 5 h. The mixture was then cooled, filtered and the residue was purified by flash column chromatography [SiO2, EtOAc] to give 2-methoxy-5-morpholin-4-yl-benzoic acid methyl ester (170 mg) as a colourless solid. (LC/MS (basic method): Rt 2.35 min, [M+H]+ 252).

Workup

  1. temperatureThe mixture was then cooled
  2. filtrationfiltered
  3. customthe residue was purified by flash column chromatography [SiO2, EtOAc]

Sources & evidence

ORD record
ord-003f43ee83234cdab93966f3b4729609
Source dataset
uspto-grants-2011_07
Patent number
US07977477B2

Reaction notes

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