Tetrahydrofuran → 1-[3-Fluoro-4-(2,2,2-trifluoro-1-hydroxy-ethyl)-phenyl]-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one

HRID 80263

Reaction equation

HRID 80263 reaction equation
C[Si](C)(C)[C:3]([F:6])([F:5])[F:4].C1COCC1.C([O-])([O-])=O.[K+].[K+].[F:20][C:21]1[CH:28]=[C:27]([N:29]2[CH2:33][CH2:32][N:31]([C:34]3[CH:35]=[N:36][CH:37]=[CH:38][C:39]=3[CH3:40])[C:30]2=[O:41])[CH:26]=[CH:25][C:22]=1[CH:23]=[O:24]>CN(C=O)C.C(Cl)(Cl)Cl.CO>[F:20][C:21]1[CH:28]=[C:27]([N:29]2[CH2:33][CH2:32][N:31]([C:34]3[CH:35]=[N:36][CH:37]=[CH:38][C:39]=3[CH3:40])[C:30]2=[O:41])[CH:26]=[CH:25][C:22]=1[CH:23]([OH:24])[C:3]([F:6])([F:5])[F:4]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 552549(Trifluoromethyl)trimethylsilaneHCID 596361642-Fluoro-4-[3-(4-methyl-pyridin-3-yl)-2-oxo-imidazolidin-1-yl]-benzaldehyde

Product 1

HCID 596362271-[3-Fluoro-4-(2,2,2-trifluoro-1-hydroxy-ethyl)-phenyl]-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-oneYield 65.92%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

0.5M solution of trimethyl-trifluoromethyl-silane in THF (6.68 mL, 3.344 mmol) and K2CO3 (250 mg, 10.82 mmol) were added to 2-fluoro-4-[3-(4-methyl-pyridin-3-yl)-2-oxo-imidazolidin-1-yl]-benzaldehyde (I-121a: 400 mg, 1.337 mmol) in dry DMF (5 mL) under nitrogen atmosphere. The resulting mixture was stirred at room temperature overnight. The reaction was monitored by TLC (5% MeOH in CHCl3). The reaction mixture was quenched with brine solution and the THF layer was concentrated. The aqueous layer was extracted with chloroform. The organic layer was dried over Na2SO4 and concentrated to get the crude product. Purification by column chromatography on silica gel (2.5% MeOH in CHCl3), followed by hexane wash, afforded 325 mg of the product (65.92% yield).

Workup

  1. customThe reaction mixture was quenched with brine solution
  2. concentrationthe THF layer was concentrated
  3. extractionThe aqueous layer was extracted with chloroform
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customto get the crude product
  7. customPurification by column chromatography on silica gel (2.5% MeOH in CHCl3)
  8. washwash

Sources & evidence

ORD record
ord-0faa4661d1c040959a9c95552cc9bdd9
Source dataset
uspto-grants-2014_09
Patent number
USRE045173E1

Linked notes

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