Ammonium Chloride → ethyl (E)-3-[2-butoxy-3'-(1-methyl-3-heptylureido)biphenyl-4-yl]-2-methylacrylate

HRID 390663Notes

Reaction equation

HRID 390663 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].[CH2:21]([NH:28][C:29](=[O:47])[N:30]([CH3:46])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=1)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl-].[NH4+]>CN(C)C=O.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:35]1[CH:34]=[CH:33][CH:32]=[C:31]([N:30]([CH3:46])[C:29]([NH:28][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:47])[CH:36]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 62657Potassium Phosphate, TribasicHCID 595749253-Heptyl-1-methyl-1-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]ureaHCID 86626086ethyl (E)-3-(3-butoxy-4-iodophenyl)-2-methylacrylate

Product 1

HCID 86626105ethyl (E)-3-[2-butoxy-3'-(1-methyl-3-heptylureido)biphenyl-4-yl]-2-methylacrylateYield 84.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 27342162-(Dicyclohexylphosphino)biphenylCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
92.5 °C

Procedure

In a manner similar to that of Example 34a, 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, 494 mg (1.7 mmol) of 3-heptyl-1-methyl-1-[3-(4,4,5,5-tetramethyl[1.3.2]dioxaborolan-2-yl)phenyl]urea 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 with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phases are combined, washed with saturated sodium chloride solution and dried over magnesium sulfate. The solvent is evaporated off and the brown oil obtained (1.3 g) is purified by chromatography on a column of silica eluted with a 70/30 heptane/ethyl acetate mixture. 558 mg (84%) of ethyl (E)-3-[2-butoxy-3′-(3-heptyl-1-methyl-ureido)biphenyl-4-yl]-2-methylacrylate are obtained.

Workup

  1. customprepared
  2. extractionextracted with ethyl acetate
  3. washwashed with saturated sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent is evaporated off
  6. customthe brown oil obtained (1.3 g)
  7. customis purified by chromatography on a column of silica
  8. washeluted with a 70/30 heptane/ethyl acetate mixture

Sources & evidence

ORD record
ord-083bf2888ae44801bfe1da2848ea4a26
Source dataset
uspto-grants-2013_02
Patent number
US08383652B2

Reaction notes

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