4-Methylmorpholine → Methyl 4-{[2-(pyridin-3-yl)ethyl]carbamoyl}benzoate

HRID 1676964Notes

Reaction equation

HRID 1676964 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1.C(Cl)(=O)C(Cl)=O.[NH2:20][CH2:21][CH2:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1.CN1CCOCC1>ClCCl.CN(C)C=O>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:5]=[CH:6][C:7]([C:8]([NH:20][CH2:21][CH2:22][C:23]2[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=2)=[O:10])=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 15513Monomethyl terephthalateHCID 65578Oxalyl chlorideHCID 8540512-(Pyridin-3-yl)ethan-1-amine

Product 1

HCID 36866255Methyl 4-{[2-(pyridin-3-yl)ethyl]carbamoyl}benzoateYield 86.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirring solution of terephthalic acid monomethyl ester (500 mg, 2.5 mmol) and oxalyl chloride (0.44 mL, 5.03 mmol) in dichloromethane (20 mL), is added 3 drops of dimethylformamide and the reaction is stirred for 2 h at room temperature. The reaction is concentrated in vacuo and then redissolved in dichloromethane. The solution is slowly added to a stirring solution of 3-(2-aminoethyl)pyridine (308 mg, 2.52 mmol) and n-methylmorpholine (0.28 mL, 2.52 mmol) in dichloromethane (20 mL). After 20 min, the reaction is washed with saturated aqueous sodium bicarbonate while extracting with 10% isopropanol/dichloromethane. The organic portion is dried with sodium sulfate, filtered, and concentrated in vacuo. The resulting residue is purified using radial chromatography, eluting with methanol and dichloromethane to obtain 613 mg (86%) of the title compound. MS (ES+) m/e 285.1 (M+1)+.

Workup

  1. concentrationThe reaction is concentrated in vacuo
  2. dissolutionredissolved in dichloromethane
  3. waitAfter 20 min
  4. washthe reaction is washed with saturated aqueous sodium bicarbonate
  5. extractionwhile extracting with 10% isopropanol/dichloromethane
  6. dry with materialThe organic portion is dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue is purified
  10. washeluting with methanol and dichloromethane

Sources & evidence

ORD record
ord-aa57b9577d29495bb59f5db7f0250f21
Source dataset
uspto-grants-2011_08
Patent number
US08008296B2

Reaction notes

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