2-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)- → 3-(3-fluoro-4-(piperidin-1-yl)phenyl)-2,6-dimethylpyrimidin-4(3H)-one

HRID 56102Notes

Reaction equation

HRID 56102 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[NH2:5].C[Al](C)C.[NH:19](/[C:23](/[CH3:29])=[CH:24]\[C:25](OC)=[O:26])[C:20]([CH3:22])=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([N:5]2[C:25](=[O:26])[CH:24]=[C:23]([CH3:29])[N:19]=[C:20]2[CH3:22])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 57053602-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)-HCID 64857583-Fluoro-4-(piperidin-1-yl)anilineHCID 16682925Trimethylaluminum

Product 1

HCID 729482103-(3-fluoro-4-(piperidin-1-yl)phenyl)-2,6-dimethylpyrimidin-4(3H)-oneYield 71.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-fluoro-4-(piperidin-1-yl)aniline (10.00 g, 51 mmol) in anhydrous CH2Cl2 (100 mL) was added trimethylaluminum (155 mL, 155 mmol, 1.0 M in toluene) under N2. The mixture was stirred at rt for 20 min, followed by the addition of a solution of methyl 3-acetaminocrotonate (9.72 g, 62 mmol) in anhydrous CH2Cl2 (20 mL). The reaction mixture was stirred at rt for 5 h, then quenched with saturated NH4Cl aqueous solution and extracted with CH2Cl2. The combined organic phases were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=2:1) to give the title compound as a pale yellow solid (11.02 g, 71%). The compound was characterized by the following spectroscopic data:

Workup

  1. stirringThe reaction mixture was stirred at rt for 5 h
  2. customquenched with saturated NH4Cl aqueous solution
  3. extractionextracted with CH2Cl2
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=2:1)

Sources & evidence

ORD record
ord-fc7574fdabc3437590a684fd78fe18f0
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

Loading…