Water → {5-[4-(1-{4-[3-(t-butyl-dimethyl-silanyloxy)-4,4-dimethyl-pentyl]-3-methyl-phenyl}-1-ethyl-propyl)-2-methyl-phenyl]-pyridin-3-yl}-acetic Acid Methyl Ester

HRID 546846Notes

Reaction equation

HRID 546846 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].[CH3:44][O:45][C:46](=[O:55])[CH2:47][C:48]1[CH:49]=[N:50][CH:51]=[C:52](Br)[CH:53]=1.O>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:44][O:45][C:46](=[O:55])[CH2:47][C:48]1[CH:49]=[N:50][CH:51]=[C:52]([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:53]=1

Participants

6

Reactant 3

HCID 962WaterHCID 23398394Methyl 2-(5-bromopyridin-3-yl)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 57709181{5-[4-(1-{4-[3-(t-butyl-dimethyl-silanyloxy)-4,4-dimethyl-pentyl]-3-methyl-phenyl}-1-ethyl-propyl)-2-methyl-phenyl]-pyridin-3-yl}-acetic Acid Methyl EsterYield 76%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 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 24-(1); 22.0 mg, 0.036 mmol) in N,N-dimethylformamide (0.3 mL) was added to 5-bromopyridine-3-acetic acid methyl ester (Example 24-(2); 19.2 mg, 0.083 mmol) and a [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II), dichloromethane complex (1:1) (3.2 mg, 0.0039 mmol). After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 76 to 84° C. for five hours and 30 minutes. Water was added to the reaction mixture, followed by extraction with ether. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate=4/1) to give the title compound (17.2 mg, 76%).

Workup

  1. temperatureAfter replacement with nitrogen, the mixture was heated
  2. extractionfollowed by extraction with ether
  3. dry with materialThe extract was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography (hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-819940af83f44b36b9b8a41625c0af50
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

Loading…