Potassium Phosphate, Tribasic → [2-(4-{1-ethyl-1-[4-((E)-3-ethyl-3-hydroxy-1-pentenyl)-3-methyl-phenyl]-propyl}-2-methyl-phenyl)-pyrimidin-5-yl]-acetic Acid Ethyl Ester

HRID 546961Notes

Reaction equation

HRID 546961 reaction equation
[CH2:1]([C:3]([OH:36])([CH2:34][CH3:35])/[CH:4]=[CH:5]/[C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH2:31][CH3:32])([C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[C:17]([CH3:30])[CH:16]=2)[CH2:13][CH3:14])=[CH:8][C:7]=1[CH3:33])[CH3:2].[CH2:37]([O:39][C:40](=[O:49])[CH2:41][C:42]1[CH:43]=[N:44][C:45](Br)=[N:46][CH:47]=1)[CH3:38].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.O>[CH2:37]([O:39][C:40](=[O:49])[CH2:41][C:42]1[CH:43]=[N:44][C:45]([C:18]2[CH:19]=[CH:20][C:15]([C:12]([CH2:13][CH3:14])([C:9]3[CH:10]=[CH:11][C:6](/[CH:5]=[CH:4]/[C:3]([CH2:34][CH3:35])([OH:36])[CH2:1][CH3:2])=[C:7]([CH3:33])[CH:8]=3)[CH2:31][CH3:32])=[CH:16][C:17]=2[CH3:30])=[N:46][CH:47]=1)[CH3:38]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 57443494Ethyl 2-(2-bromopyrimidin-5-yl)acetateHCID 57463789(E)-3-ethyl-1-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1-penten-3-ol

Product 1

HCID 57709187[2-(4-{1-ethyl-1-[4-((E)-3-ethyl-3-hydroxy-1-pentenyl)-3-methyl-phenyl]-propyl}-2-methyl-phenyl)-pyrimidin-5-yl]-acetic Acid Ethyl EsterYield 53%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Degassed N,N-dimethylformamide (0.63 mL) was added to (E)-3-ethyl-1-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1-penten-3-ol (Example 28; 52.6 mg, 0.107 mmol), 2-bromopyrimidine-5-acetic acid ethyl ester (Example 43-(3); 63 mg, 0.26 mmol), tetrakis(triphenylphosphine)palladium (0) (62.8 mg, 0.0543 mmol) and potassium phosphate (75 mg, 0.35 mmol). After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 96 to 104° C. for 13 hours. Water was added to the reaction mixture, followed by extraction with diethyl 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=3/1) to give the title compound (30 mg, 53%).

Workup

  1. customDegassed N,N-dimethylformamide (0.63 mL)
  2. temperatureAfter replacement with nitrogen, the mixture was heated
  3. extractionfollowed by extraction with diethyl ether
  4. dry with materialThe extract was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-fba4accaec12495e8fcfd804eabd1241
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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