Acetic Acid → Diethyl 2-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-2-[(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)methyl]malonate

HRID 2416010Notes

Reaction equation

HRID 2416010 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:5]([CH:14]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:6][CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1.Br[CH2:26][N:27]1[C:31](=[O:32])[C:30]2=[CH:33][CH:34]=[CH:35][CH:36]=[C:29]2[C:28]1=[O:37].C(O)(=O)C>CN(C)C=O.O>[Cl:3][C:4]1[C:5]([C:14]([CH2:26][N:27]2[C:31](=[O:32])[C:30]3[C:29](=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:28]2=[O:37])([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:6][CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 792441H-Isoindole-1,3(2H)-dione, 2-(bromomethyl)-HCID 2774041Diethyl 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)malonate

Product 1

HCID 22637220Diethyl 2-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-2-[(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)methyl]malonate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of 60% sodium hydride (0.65 g) in dry dimethylformamide (20 ml) at 0° C. was added a solution of diethyl 2-(3-chloro-5-trifluoromethyl-2-pyridyl)malonate (5 g) in dry dimethylformamide (10 ml) and the mixture was stirred for 15 minutes. A solution of N-bromomethylphthalimide (3.55 g) in dry dimethylformamide (10 ml) was added dropwise and the mixture was warmed with stirring to 22° C. over 18 hours. Glacial acetic acid (1 ml) was added and the mixture was poured into cold water (500 ml). The aqueous solution was extracted with diethyl ether (3×150 ml) and the combined extract was water washed (3×100 ml). The organic extract was dried (MgSO4) and evaporated to give a crude product. Trituration with diethyl ether/light petroleum (b.p. 40-60° C.) (1:1) gave the title compound, m.p. 159-61° C.

Workup

  1. temperaturethe mixture was warmed
  2. stirringwith stirring to 22° C. over 18 hours
  3. extractionThe aqueous solution was extracted with diethyl ether (3×150 ml)
  4. extractionthe combined extract
  5. washwashed (3×100 ml)
  6. extractionThe organic extract
  7. dry with materialwas dried (MgSO4)
  8. customevaporated
  9. customto give a crude product

Sources & evidence

ORD record
ord-f1aba7d4c4da4213b07d2f2faed38b17
Source dataset
uspto-grants-2004_11
Patent number
US06821992B1

Reaction notes

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