Potassium Acetate → HCID 178518457, compound

HRID 474779Notes

Reaction equation

HRID 474779 reaction equation
OS(C(F)(F)F)(=O)=O.[C:9](=[NH:32])([O:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([C:28]([F:31])([F:30])[F:29])[CH:22]=2)=[CH:16][CH:15]=1)[NH2:10].[OH:33]/[CH:34]=[C:35](/[CH2:40][C:41]1[CH:42]=[N:43][CH:44]=[N:45][CH:46]=1)\[C:36](OC)=O.C([O-])(=O)C.[K+]>C1(C)C=CC=CC=1>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([O:20][C:17]2[CH:16]=[CH:15][C:14]([CH2:13][CH2:12][O:11][C:9]3[NH:10][CH:36]=[C:35]([CH2:40][C:41]4[CH:46]=[N:45][CH:44]=[N:43][CH:42]=4)[C:34](=[O:33])[N:32]=3)=[CH:19][CH:18]=2)=[CH:22][C:23]=1[C:28]([F:31])([F:30])[F:29]

Participants

5

Reactant 3

HCID 517044Potassium AcetateHCID 67774726(Z)-methyl 3-hydroxy-2-(pyrimidin-5-ylmethyl)acrylateHCID 866661912-(4-{[4-Chloro-3-(trifluoromethyl)phenyl]oxy}phenyl)ethyl imidocarbamate triflate

Product 1

HCID 178518457HCID 178518457, compoundYield 21.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

An alternative synthesis was provided to prepare the compound of Example 20. A suspension of 2-(4-{[4-chloro-3-(trifluoromethyl)phenyl]oxy}phenyl)ethyl imidocarbamate triflate (17.29 g, 34.0 mmol), methyl (2Z)-3-hydroxy-2-(5-pyrimidinylmethyl)-2-propenoate (5.5 g, 28.3 mmol) and potassium acetate (5.56 g, 56.6 mmol) in toluene (200 mL) was stirred at room temperature for 2 min. and then heated to reflux for 3 h. The mixture was filtered off and concentrated to dryness, which was then dissolved in DMF and purified by MDAP with TFA. The purified fractions were combined and neutrallized with ammonia. The organic solvent was removed under vacuo and the water layer was extracted with EA. The organic layer was combined and dried over Na2SO4 which was concentrated to give the white solid. The solid was recrystallized in MeCN to afford the title compound (3.0 g, 21.06% yield) LCMS: rt=3.43 min, [M+H+]=503.

Workup

  1. customAn alternative synthesis
  2. customwas provided
  3. temperatureheated
  4. temperatureto reflux for 3 h
  5. filtrationThe mixture was filtered off
  6. concentrationconcentrated to dryness, which
  7. dissolutionwas then dissolved in DMF
  8. custompurified by MDAP with TFA
  9. customThe organic solvent was removed under vacuo
  10. extractionthe water layer was extracted with EA
  11. dry with materialdried over Na2SO4 which
  12. concentrationwas concentrated
  13. customto give the white solid
  14. customThe solid was recrystallized in MeCN

Sources & evidence

ORD record
ord-a6061ad4f1f345efb0a2f562a0745352
Source dataset
uspto-grants-2014_01
Patent number
US08637536B2

Reaction notes

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