Citric Acid → HCID 57951702, compound

HRID 1927637Notes

Reaction equation

HRID 1927637 reaction equation
C(NC(C1C=CC([O:12][C:13]2[C:18]([F:19])=[CH:17][C:16]([CH2:20][C:21]([O:23]C)=[O:22])=[C:15]([F:25])[CH:14]=2)=C([N+]([O-])=O)C=1)=O)(C)(C)C.C(NC(=O)C1C=CC(Cl)=C([N+]([O-])=O)C=1)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O.C(OCC)(=O)C>[F:25][C:15]1[CH:14]=[C:13]([OH:12])[C:18]([F:19])=[CH:17][C:16]=1[CH2:20][C:21]([OH:23])=[O:22]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 10796Cesium carbonateHCID 1101333HCID 1101333, compoundHCID 57951700HCID 57951700, compound

Product 1

HCID 57951702HCID 57951702, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 2-(4-(4-(tert-butylcarbamoyl)-2-nitrophenoxy)-2,5-difluorophenyl)acetate (A.6) To a solution of compound A.4 (500 mg, 2.66 mmol) and N-tert-butyl-4-chloro-3-nitrobenzamide (A.5) (682 mg, 2.66 mmol) in DMSO (25 ml), Cs2CO3 (1.73 g, 5.32 mmol) was added in one portion. The reaction mixture was stirred at 80° C. for 1 hour, diluted with ethyl acetate and then 10% citric acid was added to adjust pH=2. The aqueous layer was extracted with ethyl acetate (2×), the combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in methanol (10 ml) then chlorotrimethylsilane was added to the solution. The reaction was stirred at room temperature for 1 hour and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, 30% ethyl acetate in hexane.eluent) to give compound A.6 (340 mg, 30%, 2 steps). LC-MS ESI (pos.) m/z: 423.1 (M+H).

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  2. washthe combined organic layers were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in methanol (10 ml)
  6. additionchlorotrimethylsilane was added to the solution
  7. stirringThe reaction was stirred at room temperature for 1 hour
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography (silica gel, 30% ethyl acetate in hexane.eluent)
  10. customto give compound A.6 (340 mg, 30%, 2 steps)

Sources & evidence

ORD record
ord-4a3a8351207d40d7bb3afc7ae1679ad6
Source dataset
uspto-grants-2012_05
Patent number
US08183293B2

Reaction notes

Loading…