Water → Methyl 3-[3-fluoro-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]acrylate

HRID 250822Notes

Reaction equation

HRID 250822 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]([O:12][CH3:13])=[O:11])=[C:4]([F:14])[CH:3]=1.[CH2:15]([NH:22][C:23](=[O:41])[N:24]([CH3:40])[C:25]1[CH:30]=[CH:29][CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].O>CN(C)C=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:14][C:4]1[CH:3]=[C:2]([C:29]2[CH:28]=[CH:27][CH:26]=[C:25]([N:24]([CH3:40])[C:23]([NH:22][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[O:41])[CH:30]=2)[CH:7]=[CH:6][C:5]=1[CH:8]=[CH:9][C:10]([O:12][CH3:13])=[O:11]

Participants

7

Reactant 3

HCID 962WaterHCID 54485126Methyl 3-(4-bromo-2-fluorophenyl)-2-propenoateHCID 595749253-Heptyl-1-methyl-1-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]urea

Product 1

HCID 67271956Methyl 3-[3-fluoro-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]acrylateYield 42%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
90 °C

Procedure

44 mg (5 mol %) of tetrakis(triphenylphosphine)palladium are added to a solution of 200 mg (0.77 mmol, 1.0 eq) of methyl 3-(4-bromo-2-fluorophenyl)acrylate and 430 mg (1.15 mmol, 1.5 eq) of 3-heptyl-1-methyl-1-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]urea (prepared as in 1e) in a mixture of dimethylformamide and 2M potassium phosphate solution (8/2). The reaction mixture is stirred for 2 hours at 90° C. The reaction is stopped by addition of 10 mL of water and then extracted with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then chromatographed on silica gel (70/30 heptane/ethyl acetate). 138 mg of methyl 3-[3-fluoro-3′-(3-heptyl-1-methylureido)biphenyl-4-yl]acrylate are obtained. Yield=42%

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialdried over sodium sulfate
  3. customThe solvents are evaporated off
  4. customthe residue is then chromatographed on silica gel (70/30 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-021f43fab3d14ddd87077b5c00f38d00
Source dataset
uspto-grants-2011_01
Patent number
US07863332B2

Reaction notes

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