Ammonium Chloride → {5-[4-(1-ethyl-1-{3-methyl-4-[2-(1-trimethylsilanyloxy-cyclopentyl)-ethyl]-phenyl}-propyl)-2-methyl-phenyl]-pyridin-3-yl}-acetic Acid Methyl Ester

HRID 547004Notes

Reaction equation

HRID 547004 reaction equation
[CH2:1]([C:3]([C:25]1[CH:30]=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[C:27]([CH3:40])[CH:26]=1)([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][C:14]2([O:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH2:18][CH2:17][CH2:16][CH2:15]2)=[C:8]([CH3:24])[CH:7]=1)[CH2:4][CH3:5])[CH3:2].[CH3:41][O:42][C:43](=[O:52])[CH2:44][C:45]1[CH:46]=[N:47][CH:48]=[C:49](Br)[CH:50]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl-].[NH4+]>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.O.CN(C)C=O>[CH3:41][O:42][C:43](=[O:52])[CH2:44][C:45]1[CH:46]=[N:47][CH:48]=[C:49]([C:28]2[CH:29]=[CH:30][C:25]([C:3]([CH2:4][CH3:5])([C:6]3[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][C:14]4([O:19][Si:20]([CH3:22])([CH3:23])[CH3:21])[CH2:18][CH2:17][CH2:16][CH2:15]4)=[C:8]([CH3:24])[CH:7]=3)[CH2:1][CH3:2])=[CH:26][C:27]=2[CH3:40])[CH:50]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 62657Potassium Phosphate, TribasicHCID 23398394Methyl 2-(5-bromopyridin-3-yl)acetateHCID 577089962-[4-(1-Ethyl-1-{3-methyl-4-[2-(1-trimethylsilanyloxy-cyclopentyl)-ethyl]-phenyl}-propyl)-2-methyl-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

Product 1

HCID 57709005{5-[4-(1-ethyl-1-{3-methyl-4-[2-(1-trimethylsilanyloxy-cyclopentyl)-ethyl]-phenyl}-propyl)-2-methyl-phenyl]-pyridin-3-yl}-acetic Acid Methyl EsterYield 72.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

2-[4-(1-ethyl-1-{3-methyl-4-[2-(1-trimethylsilanyloxy-cyclopentyl)-ethyl]-phenyl}-propyl)-2-methyl-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Example 34-(1); 35.7 mg, 0.063 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 19.0 mg, 0.082 mmol), tetrakis(triphenylphosphine)palladium (0) (9.2 mg, 0.080 mmol), potassium phosphate (26.3 mg, 0.124 mmol) and N,N-dimethylformamide (0.38 mL) were placed in a reaction vessel and stirred in a nitrogen atmosphere at 95° C. for three hours. A saturated aqueous ammonium chloride solution (0.1 mL) and water (0.1 mL) were added to the reaction mixture, followed by extraction with diethyl ether. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane only to hexane/ethyl acetate=3/1) to give the title compound (26.8 mg, 72%).

Workup

  1. extractionfollowed by extraction with diethyl ether
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel chromatography (hexane only to hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-7970abd1e6f142c6ab31d5958747b4fb
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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