Potassium Phosphate, Tribasic → HCID 16224622, compound

HRID 1808305Notes

Reaction equation

HRID 1808305 reaction equation
[CH2:1]([O:5][C:6]1[CH:7]=[C:8](/[CH:20]=[C:21](\[O:25][CH3:26])/[C:22]([OH:24])=[O:23])[CH:9]=[CH:10][C:11]=1OS(C(F)(F)F)(=O)=O)[CH2:2][CH2:3][CH3:4].[CH2:27]([NH:34][C:35](=[O:53])[N:36]([CH3:52])[C:37]1[CH:42]=[CH:41][CH:40]=[C:39](B2OC(C)(C)C(C)(C)O2)[CH:38]=1)[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:5][C:6]1[CH:7]=[C:8](/[CH:20]=[C:21](\[O:25][CH3:26])/[C:22]([OH:24])=[O:23])[CH:9]=[CH:10][C:11]=1[C:41]1[CH:40]=[CH:39][CH:38]=[C:37]([N:36]([CH3:52])[C:35]([NH:34][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])=[O:53])[CH:42]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 595749253-Heptyl-1-methyl-1-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]ureaHCID 86647490HCID 86647490, compound

Product 1

HCID 16224622HCID 16224622, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

870 g (2.2 mmol) of (Z)-3-(3-butoxy-4-(trifluoromethanesulphonyloxy)phenyl)-2-methoxyacrylic acid (XII), 981 mg (2.62 mmol) of 3-heptyl-1-methyl-1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea (III) [prepared according to International Application WO2007/049158], 14 mg (3 mol %) of palladium acetate and 46 mg (6 mol %) of dicyclohexylbiphenylphosphine are dissolved in 8 ml of dimethylformamide, 1.5 ml of a 2M potassium phosphate solution are added and the medium is degassed several times. The reaction mixture is stirred at 90° C. for 2 hours. The reaction is halted with a 2M hydrochloric acid solution and then the mixture is extracted with ethyl acetate. The organic phases are washed with a sodium chloride solution and then dried over Na2SO4. The solvents are evaporated and then the residue is taken up in 10 ml of heptane/AcOEt 1/1. Filtration is carried out through a silica patch (1 cm). The solvents are evaporated. The residue is precipitated from pentane. The solid is recrystallized from isopropyl ether/heptane. 510 mg of (Z)-3-[2-butoxy-3′-(3-heptyl-1-methylureido)biphenyl-4-yl]-2-methoxyacrylic acid are obtained in the solid form.

Workup

  1. customthe medium is degassed several times
  2. extractionthe mixture is extracted with ethyl acetate
  3. washThe organic phases are washed with a sodium chloride solution
  4. dry with materialdried over Na2SO4
  5. customThe solvents are evaporated
  6. filtrationFiltration
  7. customThe solvents are evaporated
  8. customThe residue is precipitated from pentane
  9. customThe solid is recrystallized from isopropyl ether/heptane

Sources & evidence

ORD record
ord-13075f6726b844c68572c754ce98a440
Source dataset
uspto-grants-2013_01
Patent number
US08357819B2

Reaction notes

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