Potassium Phosphate, Tribasic → Ethyl 2-[1-[2-butoxy-3'-(1-methyl-3-pentylureido)biphenyl-4-yl]meth-(e)-ylidene]butyrate

HRID 390665Notes

Reaction equation

HRID 390665 reaction equation
[CH2:1]([O:5][C:6]1[CH:7]=[C:8](/[CH:13]=[C:14](\[CH2:20][CH3:21])/[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:9]=[CH:10][C:11]=1I)[CH2:2][CH2:3][CH3:4].[CH3:22][N:23]([C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1)[C:24]([NH:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[O:25].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](\[CH2:20][CH3:21])/[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:9]=[CH:10][C:11]=1[C:34]1[CH:35]=[CH:36][CH:37]=[C:32]([N:23]([CH3:22])[C:24]([NH:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[O:25])[CH:33]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 672732723-(1-Methyl-3-pentylureido)phenylboronic acidHCID 68957093Ethyl 2-[1-(3-butoxy-4-iodophenyl)meth-(e)-ylidene]butyrate

Product 1

HCID 68964170Ethyl 2-[1-[2-butoxy-3'-(1-methyl-3-pentylureido)biphenyl-4-yl]meth-(e)-ylidene]butyrateYield 76%

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 523 mg (1.3 mmol) of ethyl 2-[1-(3-butoxy-4-iodophenyl)meth-(E)-ylidene]butyrate (prepared according to Example 22a), 446 mg (1.7 mmol) of 3-(1-methyl-3-pentylureido)phenylboronic acid (prepared according to 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 sodium chloride solution and dried over magnesium sulfate. After filtration, the solvent is evaporated off and the brown oil obtained (1.2 g) is purified by chromatography on a column of silica eluted with a 70/30 heptane/ethyl acetate mixture. 489 mg (76%) of ethyl 2-[1-[2-butoxy-3′-(1-methyl-3-pentylureido)biphenyl-4-yl]meth-(E)-ylidene]butyrate are obtained.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with saturated sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. filtrationAfter filtration
  5. customthe solvent is evaporated off
  6. customthe brown oil obtained (1.2 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-69ccf208a7874709b0f5164158eb0842
Source dataset
uspto-grants-2013_02
Patent number
US08383652B2

Reaction notes

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