Ammonium Chloride → Ethyl 2-[1-[2-butoxy-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]meth-(e)-ylidene]butyrate

HRID 390667Notes

Reaction equation

HRID 390667 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].[CH2:22]([NH:29][C:30](=[O:48])[N:31]([CH3:47])[C:32]1[CH:37]=[CH:36][CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=1)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].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](\[CH2:20][CH3:21])/[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:9]=[CH:10][C:11]=1[C:36]1[CH:35]=[CH:34][CH:33]=[C:32]([N:31]([CH3:47])[C:30]([NH:29][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[O:48])[CH:37]=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 68957093Ethyl 2-[1-(3-butoxy-4-iodophenyl)meth-(e)-ylidene]butyrate

Product 1

HCID 68959502Ethyl 2-[1-[2-butoxy-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]meth-(e)-ylidene]butyrateYield 79%

Reagents, catalysts & solvents 3

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

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 as described in Example 22a), 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 (prepared according to Example 35b) and 1.3 mL of aqueous 2M 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 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 (1.3 g) is purified by chromatography on a column of silica eluted with a 70/30 heptane/ethyl acetate mixture. 537 mg (79%) of ethyl 2-[1-[2-butoxy-3′-(3-heptyl-1-methylureido)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 (1.3 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-adf5a0f577864956a308da4c03566a37
Source dataset
uspto-grants-2013_02
Patent number
US08383652B2

Reaction notes

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