Citric Acid → HCID 53311953, compound

HRID 1966985Notes

Reaction equation

HRID 1966985 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:3]=1[O:4][C:5]1[C:10]([C:11]([NH:13][C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[O:21][CH3:22])=[O:12])=[CH:9][N:8]=[CH:7][CH:6]=1.[CH3:28]C(C)([O-])C.[K+].IC.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:3]=1[O:4][C:5]1[C:10]([C:11]([N:13]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[O:21][CH3:22])[CH3:28])=[O:12])=[CH:9][N:8]=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 6328Methyl iodideHCID 23665647Potassium tert-butoxideHCID 67320747HCID 67320747, compound

Product 1

HCID 53311953HCID 53311953, compoundYield 44.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cold suspension of 0.07 g (0.17 mmol) 4-(2,5-dichloro-phenoxy)-N-(5-fluoro-2-methoxy-phenyl)-nicotinamide in 1 mL tetrahydrofuran were added 0.019 g (0.17 mmol) potassium tert-butoxide followed by 10 μl (0.18 mmol) iodomethane. The suspension was stirred at room temperature for 16 hours, poured onto 10% aqueous citric acid solution and was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, treated with silica gel and evaporated to dryness. The resulting powder was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50) to give 32 mg (44%) of the title compound as a white solid. MS (ESI): m/z=421.052 [M+H]+.

Workup

  1. extractionwas extracted three times with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. additiontreated with silica gel
  6. customevaporated to dryness
  7. customThe resulting powder was purified by silica gel chromatography
  8. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50)

Sources & evidence

ORD record
ord-bfe9b4424d554f37a86b06d0397df444
Source dataset
uspto-grants-2013_04
Patent number
US08420647B2

Reaction notes

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