Acetonitrile → Ethyl 2-fluoro-3-({[2-(morpholin-4-yl)pyrimidin-5-yl]oxy}methyl)benzoate

HRID 1021266Notes

Reaction equation

HRID 1021266 reaction equation
[N:1]1([C:7]2[N:12]=[CH:11][C:10]([OH:13])=[CH:9][N:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:15][C:16]1[C:17]([F:27])=[C:18]([CH:24]=[CH:25][CH:26]=1)[C:19]([O:21][CH2:22][CH3:23])=[O:20].CC#N.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C1COCC1>[F:27][C:17]1[C:16]([CH2:15][O:13][C:10]2[CH:11]=[N:12][C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[N:8][CH:9]=2)=[CH:26][CH:25]=[CH:24][C:18]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 198710352-(4-morpholinyl)-5-PyrimidinolHCID 58009396Ethyl 3-(bromomethyl)-2-fluorobenzoate

Product 1

HCID 86686214Ethyl 2-fluoro-3-({[2-(morpholin-4-yl)pyrimidin-5-yl]oxy}methyl)benzoateYield 63.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-(Morpholin-4-yl)pyrimidin-5-ol (300 mg) and ethyl 3-(bromomethyl)-2-fluorobenzoate (850 mg) were mixed with MeCN (5 ml), THF (2 ml) and DMF (1 ml), and potassium carbonate was added thereto, followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and EtOAc and water were then added thereto. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain ethyl 2-fluoro-3-({[2-(morpholin-4-yl)pyrimidin-5-yl]oxy}methyl)benzoate (378 mg).

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure, and EtOAc and water
  3. additionwere then added
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-496f576c673e4153ad79fa8601bdf548
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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