Morpholine → 4-(2-Fluorophenyl)-6-methyl-2-morpholin-4-yl-pyrimidine-5-carboxylic acid ethyl ester

HRID 883013Notes

Reaction equation

HRID 883013 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:18]([CH3:25])[NH:17][C:16](=O)[N:15]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>O1CCOCC1.CCOC(C)=O>[CH2:23]([O:22][C:20]([C:19]1[C:14]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[F:7])=[N:15][C:16]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[N:17][C:18]=1[CH3:25])=[O:21])[CH3:24]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 2733179PyBroPHCID 59421129Ethyl 4-(2-fluorophenyl)-1,2-dihydro-6-methyl-2-oxopyrimidine-5-carboxylate

Product 1

HCID 594212924-(2-Fluorophenyl)-6-methyl-2-morpholin-4-yl-pyrimidine-5-carboxylic acid ethyl esterYield 64%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Morpholine (0.5 mL) was added to a stirred solution of ethyl 4-(2-fluorophenyl)-1,2-dihydro-6-methyl-2-oxopyrimidine-5-carboxylate (0.75 g, 2.72 mmol), PyBroP (1.4 g, 3 mmol), and triethylamine (1 mL) in 1,4-dioxane (20 mL) at room temperature. The solution was stirred at room temperature for 3 h and diluted with EtOAc. The solution was washed with saturated NH4Cl and saturated aqueous NaCl solution, and dried. The solvent was removed under reduced pressure, and the residue was purified by Biotage SP1 on packed silica gel column (5%-80% EtOAC/hexanes gradient) to give 4-(2-fluorophenyl)-6-methyl-2-morpholin-4-yl-pyrimidine-5-carboxylic acid ethyl ester as an oil (0.937 g, 64%). Mass Spec. LCMS 346 (M+1).

Workup

  1. washThe solution was washed with saturated NH4Cl and saturated aqueous NaCl solution
  2. customdried
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by Biotage SP1

Sources & evidence

ORD record
ord-5eadd08b976a40d889c5e7af0bff3612
Source dataset
uspto-grants-2012_08
Patent number
US08236815B2

Reaction notes

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