Sodium hydride → 1-(4-Pyridyl)-3-[6-[4-(trifluoromethyl)phenoxy]hexyl]imidazolidin-2-one

HRID 49259Notes

Reaction equation

HRID 49259 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:11][CH2:10][NH:9][C:8]2=[O:12])=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1>CN(C=O)C>[N:1]1[CH:2]=[CH:3][C:4]([N:7]2[CH2:11][CH2:10][N:9]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][O:22][C:23]3[CH:24]=[CH:25][C:26]([C:29]([F:30])([F:31])[F:32])=[CH:27][CH:28]=3)[C:8]2=[O:12])=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 37468181-Pyridin-4-yl-imidazolidin-2-oneHCID 129864901-Bromo-6-[4-(trifluoromethyl)-phenoxy]hexane

Product 1

HCID 4930801-(4-Pyridyl)-3-[6-[4-(trifluoromethyl)phenoxy]hexyl]imidazolidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of 1-(4-pyridyl)-2-imidazolidinone (0.10 g, 0.61 mmol) and sodium hydride (75% dispersion in mineral oil, 0.02 g, 0.67 mmol) in anhydrous DMF (7 mL) was cooled in an ice bath and stirred at 0° C. for 30 minutes, followed by addition of a solution of 1-bromo-6-[4-(trifluoromethyl)-phenoxy]hexane (0.20 g, 0.61 mmol) in anhydrous DMF (3 mL). After 5 minutes, the ice bath was removed and the reaction mixture was stirred at room temperature for 3 hours. The reaction was quenched with a saturated aqueous ammonium chloride solution followed by extraction with a mixture of diethyl ether and ethyl acetate (3:1, 100 mL×3). The organic layers were combined and washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The crude mixture thus obtained was purified with gradient chromatography [100% ethyl acetate, and, subsequently, a mixture of ethyl acetate and methanol (4:1)] to yield the product (i.e., Compound 1) as a white solid (0.18 g, 73%).

Workup

  1. temperaturewas cooled in an ice bath
  2. waitAfter 5 minutes
  3. customthe ice bath was removed
  4. stirringthe reaction mixture was stirred at room temperature for 3 hours
  5. customThe reaction was quenched with a saturated aqueous ammonium chloride solution
  6. extractionfollowed by extraction with a mixture of diethyl ether and ethyl acetate (3:1, 100 mL×3)
  7. washwashed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe crude mixture thus obtained
  11. customwas purified with gradient chromatography [100% ethyl acetate
  12. additionsubsequently, a mixture of ethyl acetate and methanol (4:1)]

Sources & evidence

ORD record
ord-b0d0f4b1855e4e5184ce0985ce2f477d
Source dataset
uspto-grants-2004_03
Patent number
US06706739B2

Reaction notes

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