Morpholine → methyl 3-(morpholin-4-ylmethyl)benzoate

HRID 1174502Notes

Reaction equation

HRID 1174502 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(N(CC)CC)C.Br[CH2:15][C:16]1[CH:17]=[C:18]([CH:23]=[CH:24][CH:25]=1)[C:19]([O:21][CH3:22])=[O:20]>CCO.Cl>[N:1]1([CH2:15][C:16]2[CH:17]=[C:18]([CH:23]=[CH:24][CH:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 517981Methyl 3-(bromomethyl)benzoate

Product 1

HCID 437850methyl 3-(morpholin-4-ylmethyl)benzoateYield 70.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent

Procedure

To a solution of morpholine (80 g, 0.91 mol) and triethylamine (232 g, 2.29 mol) in EtOH (1750 ml) was added dropwise at 0° C. a solution of methyl 3-(bromomethyl)benzoate (252 g, 1.1034 mol) in absolute alcohol (250 ml). The mixture was stirred overnight at RT. Then the mixture was concentrated and the residue obtained was taken up in 1.5N HCl (3 L) then washed with diethyl ether (3 times) and ethyl acetate. The solution was neutralized with a 10% aqueous NaOH solution and basified up to pH=8 with a 10% aqueous NaHCO3 solution. The product was extracted with CHCl3, washed with water and brine then dried over Na2SO4. The solvent was removed and the crude was purified by column chromatography CHCl3/MeOH to give methyl 3-(morpholin-4-ylmethyl)benzoate (150 g, 70%) as brown liquid.

Workup

  1. concentrationThen the mixture was concentrated
  2. customthe residue obtained
  3. washthen washed with diethyl ether (3 times) and ethyl acetate
  4. extractionThe product was extracted with CHCl3
  5. washwashed with water and brine
  6. dry with materialthen dried over Na2SO4
  7. customThe solvent was removed
  8. customthe crude was purified by column chromatography CHCl3/MeOH

Sources & evidence

ORD record
ord-e188e3305c8e40738196f40f4be01150
Source dataset
uspto-grants-2010_11
Patent number
US07838522B2

Reaction notes

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