Potassium Phosphate, Tribasic → ethyl (E)-3-[2-butoxy-3'-(1-methyl-3-pentylureido)biphenyl-4-yl]-2-methylacrylate

HRID 390660Notes

Reaction equation

HRID 390660 reaction equation
[CH2:1]([O:5][C:6]1[CH:7]=[C:8](/[CH:13]=[C:14](\[CH3:20])/[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:9]=[CH:10][C:11]=1I)[CH2:2][CH2:3][CH3:4].[CH3:21][N:22]([C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1)[C:23]([NH:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[O:24].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.[Cl-].[NH4+].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>[CH2:1]([O:5][C:6]1[CH:7]=[C:8](/[CH:13]=[C:14](\[CH3:20])/[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:9]=[CH:10][C:11]=1[C:33]1[CH:34]=[CH:35][CH:36]=[C:31]([N:22]([CH3:21])[C:23]([NH:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[O:24])[CH:32]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 672732723-(1-Methyl-3-pentylureido)phenylboronic acidHCID 86626086ethyl (E)-3-(3-butoxy-4-iodophenyl)-2-methylacrylate

Product 1

HCID 86626104ethyl (E)-3-[2-butoxy-3'-(1-methyl-3-pentylureido)biphenyl-4-yl]-2-methylacrylateYield 85.3%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 27342162-(Dicyclohexylphosphino)biphenylCatalystHCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
92.5 °C

Procedure

3 mg (0.013 mmol) of palladium acetate and then 9 mg (0.026 mmol) of 2-(dicyclohexylphosphino)biphenyl are added to a mixture of 505 mg (1.3 mmol) of ethyl (E)-3-(3-butoxy-4-iodophenyl)-2-methylacrylate prepared as described in Example 19h, 446 mg (1.7 mmol) of 3-(1-methyl-3-pentylureido)phenylboronic acid prepared as described in Example 24h and 1.3 mL of aqueous 2 M potassium phosphate solution in 6.5 mL of dimethylformamide. The reaction mixture is heated at 90-95° C. for 2 hours. The reaction medium is hydrolyzed in saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phases are combined, washed with saturated aqueous sodium chloride solution and dried over magnesium sulfate. After filtration, the solvent is evaporated off and the brown oil obtained (1.5 g) is purified by chromatography on a column of silica eluted with a 70/30 heptane/ethyl acetate mixture. 533 mg (85%) of ethyl (E)-3-[2-butoxy-3′-(1-methyl-3-pentylureido)biphenyl-4-yl]-2-methylacrylate are obtained.

Workup

  1. customprepared
  2. customprepared
  3. extractionextracted with ethyl acetate
  4. washwashed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationAfter filtration
  7. customthe solvent is evaporated off
  8. customthe brown oil obtained (1.5 g)
  9. customis purified by chromatography on a column of silica
  10. washeluted with a 70/30 heptane/ethyl acetate mixture

Sources & evidence

ORD record
ord-7ad05b2ecb41461d972747008f1fb3dc
Source dataset
uspto-grants-2013_02
Patent number
US08383652B2

Reaction notes

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