Potassium Phosphate, Tribasic → [4'-(1-{4-[3-(t-butyl-dimethyl-silanyloxy)-4,4-dimethyl-pentyl]-3-methyl-phenyl}-1-ethyl-propyl)-3-fluoro-2'-methyl-biphenyl-4-yl]-acetic Acid Methyl Ester

HRID 546912Notes

Reaction equation

HRID 546912 reaction equation
[C:1]([Si:5]([O:8][CH:9]([CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([CH2:41][CH3:42])([C:25]2[CH:30]=[CH:29][C:28](B3OC(C)(C)C(C)(C)O3)=[C:27]([CH3:40])[CH:26]=2)[CH2:23][CH3:24])=[CH:18][C:17]=1[CH3:43])[C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:81][O:82][C:83](=[O:93])[CH2:84][C:85]1[CH:90]=[CH:89][C:88](Cl)=[CH:87][C:86]=1[F:92]>C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:81][O:82][C:83](=[O:93])[CH2:84][C:85]1[CH:90]=[CH:89][C:88]([C:28]2[CH:29]=[CH:30][C:25]([C:22]([C:19]3[CH:20]=[CH:21][C:16]([CH2:15][CH2:14][CH:9]([O:8][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:6])[CH3:7])[C:10]([CH3:13])([CH3:12])[CH3:11])=[C:17]([CH3:43])[CH:18]=3)([CH2:23][CH3:24])[CH2:41][CH3:42])=[CH:26][C:27]=2[CH3:40])=[CH:87][C:86]=1[F:92]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 57443493Methyl 2-(4-chloro-2-fluorophenyl)acetateHCID 577089262-[4-(1-{4-[3-(t-Butyldimethyl-silanyloxy)-4,4-dimethyl-pentyl]-3-methyl-phenyl}-1-ethyl-propyl)-2-methyl-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

Product 1

HCID 57708949[4'-(1-{4-[3-(t-butyl-dimethyl-silanyloxy)-4,4-dimethyl-pentyl]-3-methyl-phenyl}-1-ethyl-propyl)-3-fluoro-2'-methyl-biphenyl-4-yl]-acetic Acid Methyl EsterYield 77%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

Degassed toluene (0.12 mL) and water (0.012 mL) were added to t-butyl-(1-{2-[4-(1-ethyl-1-{4-[4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl]-3-methyl-phenyl}-propyl)-2-methyl-phenyl]-ethyl}-2,2-dimethyl-propoxy)dimethylsilane (Example 23-(1); 16.5 mg, 0.0272 mmol), palladium (II) acetate (0.9 mg, 0.004 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (3.3 mg, 0.0080 mmol) and potassium phosphate (19.0 mg, 0.0895 mmol). After replacement with nitrogen, (4-chloro-2-fluoro-phenyl)acetic acid methyl ester (Example 40; 7.4 mg, 0.037 mmol) was added. After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 96 to 104° C. for one hour. The reaction mixture was diluted with diethyl ether and filtered through cotton plug, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate=50/1) to give the title compound (13.5 mg, 77%).

Workup

  1. customDegassed toluene (0.12 mL) and water (0.012 mL)
  2. temperatureAfter replacement with nitrogen, the mixture was heated
  3. filtrationfiltered through cotton plug
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography (hexane/ethyl acetate=50/1)

Sources & evidence

ORD record
ord-a7ad44a1193f486484bdf3276c748300
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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