Sodium Carbonate → HCID 57586506, compound

HRID 420349Notes

Reaction equation

HRID 420349 reaction equation
[CH2:1]([O:3][C:4](=[O:37])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26](Br)[CH:25]=[C:24](Br)[CH:23]=2)[C:10]=1[CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH3:2].[N:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.C(O)C.O.C(OCC)(=O)C.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>[CH2:1]([O:3][C:4](=[O:37])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([C:41]3[CH:42]=[CH:43][N:38]=[CH:39][CH:40]=3)[CH:25]=[C:24]([C:41]3[CH:42]=[CH:43][N:38]=[CH:39][CH:40]=3)[CH:23]=2)[C:10]=1[CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH3:2]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 57586569HCID 57586569, compound

Product 1

HCID 57586506HCID 57586506, compoundYield 64.2%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-{3-[6-(3,5-dibromo-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester (321 mg, 0.5 mmol) in dimethoxyethane (10 mL) was stirred for 5 minutes at room temperature under a nitrogen atmosphere. Then, tetrakis(triphenylphosphine)palladium(0) (115 mg, 0.1 mmol) was added at room temperature and the resulting light yellow solution was heated to 80° C. and stirred for 5 minutes. At this point, a solution of pyridin-4-ylboronic acid (368 mg, 3.0 mmol) in ethanol (10 mL) was added followed by a solution of sodium carbonate (318 mg, 3.0 mmol) in water (1.0 mL). The resulting light yellow suspension was stirred for 24 h at reflux. Then, the reaction mixture was cooled to room temperature and diluted with water (20 mL) and ethyl acetate (50 mL). The two layers were separated and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic extracts were washed with water (100 mL), brine solution (100 mL), and dried over anhydrous magnesium sulfate. Filtration and concentration of the solvent gave the crude residue which was purified by using an ISCO 40 g column, eluting with 0-50% ethyl acetate/hexanes to afford 4-{3-[6-(3,5-di-pyridin-4-yl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester (205 mg, 64%) as a light brown oil: ES(+)-HRMS m/e calculated for C39H46N2O6 (M+H)+ 639.3429, found 639.3426.

Workup

  1. stirringThe resulting light yellow suspension was stirred for 24 h
  2. temperatureat reflux
  3. temperatureThen, the reaction mixture was cooled to room temperature
  4. customThe two layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
  6. washThe combined organic extracts were washed with water (100 mL), brine solution (100 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationFiltration and concentration of the solvent
  9. customgave the crude residue which
  10. customwas purified
  11. washeluting with 0-50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-62670b4dd6524fb996e0515749b58c38
Source dataset
uspto-grants-2012_01
Patent number
US08093385B2

Reaction notes

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