Sodium hydride → HCID 68572139, compound

HRID 1932476Notes

Reaction equation

HRID 1932476 reaction equation
[H-].[Na+].C(C1C=CC(OC2C=CC(C(NC3C=CC(C(F)(F)F)=CC=3)=O)=CN=2)=CC=1)(=O)C.[Cl-].[NH4+].[F:34][C:35]([F:67])([F:66])[C:36]1[CH:41]=[CH:40][C:39]([NH:42][C:43]([C:45]2[CH:46]=[CH:47][C:48]([O:51][C:52]3[CH:57]=[CH:56][C:55]([C:58]([CH3:65])=[CH:59][C:60]([O:62][CH2:63][CH3:64])=[O:61])=[CH:54][CH:53]=3)=[N:49][CH:50]=2)=[O:44])=[CH:38][CH:37]=1>C1COCC1>[F:66][C:35]([F:34])([F:67])[C:36]1[CH:37]=[CH:38][C:39]([NH:42][C:43]([C:45]2[CH:46]=[CH:47][C:48]([O:51][C:52]3[CH:57]=[CH:56][C:55]([CH:58]([CH3:65])[CH2:59][C:60]([O:62][CH2:63][CH3:64])=[O:61])=[CH:54][CH:53]=3)=[N:49][CH:50]=2)=[O:44])=[CH:40][CH:41]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 18673976HCID 18673976, compoundHCID 68523790HCID 68523790, compound

Product 1

HCID 68572139HCID 68572139, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 60% sodium hydride (0.133 g, 3.3 mmol) in THF (6 mL) was added dropwise triethylphosphono acetate (0.53 mL, 2.7 mmol) under ice cooling, and the resulting solution was stirred for 1 hour at room temperature. To the reaction solution was added a solution of 6-(4-acetylphenoxy)-N-[4-(trifluoromethyl]phenyl]nicotinamide (0.53 g, 1.3 mmol) in THF (6 mL), and the resulting solution was stirred for 10 hours at 60° C. To the reaction solution was added saturated aqueous ammonium chloride, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel chromatography (n-hexane:ethyl acetate=4:1), to thereby yield 0.57 g of the intermediate product ethyl 3-(4-{5-[4-(trifluoromethyl)phenyl-carbamoyl]pyridin-2-yloxy}phenyl)-2-butenoate. 10% palladium-carbon (0.057 g) was suspended in a mixed solvent consisting of ethanol (8 mL) and dioxane (2 mL), and to this suspension was added ethyl 3-(4-{5-[4-(trifluoromethyl)phenylcarbamoyl]pyridin-2-yloxy}phenyl)-2-butenoate (0.57 g, 1.2 mmol). The resulting product was subjected to catalytic reduction at atmospheric pressure and room temperature. Once the absorption of hydrogen had stopped, the catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure, to thereby yield 0.56 g of the title compound.

Workup

  1. stirringthe resulting solution was stirred for 10 hours at 60° C
  2. extractionextracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customevaporated
  6. customthe residue was purified by silica gel chromatography (n-hexane:ethyl acetate=4:1)
  7. customwas subjected to catalytic reduction at atmospheric pressure and room temperature
  8. customOnce the absorption of hydrogen
  9. customthe catalyst was removed by filtration
  10. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-329cbd30a1cb4a7897e0e6a19546f3df
Source dataset
uspto-grants-2012_05
Patent number
US08188277B2

Reaction notes

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