Sodium Carbonate → HCID 86628186, compound

HRID 420392Notes

Reaction equation

HRID 420392 reaction equation
[CH2:1]([O:3][C:4](=[O:46])[CH:5]([O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH:6]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14]C1C=C(C2C=CC3OCCOC=3C=2)C=C(Br)C=1)[CH3:7])[CH3:2].[C:47]1(B(O)O)[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.[C:56](=[O:59])([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:46])[CH:5]([O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH:6]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:49]1[CH:48]=[C:47]([C:35]2[CH:34]=[CH:33][CH:38]=[CH:37][CH:36]=2)[CH:52]=[C:51]([C:8]2[CH:6]=[CH:5][C:4]3[O:3][CH2:1][CH2:2][O:59][C:56]=3[CH:9]=2)[CH:50]=1)[CH3:7])[CH3:2]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 86628187HCID 86628187, compound

Product 1

HCID 86628186HCID 86628186, compoundYield 90.6%

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-bromo-5-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-phenoxy]-hexyl}-(2-(2-ethoxycarbonyl-ethyl)-phenoxy)-butyric acid ethyl ester (189 mg, 0.27 mmol) in dimethoxyethane (5 mL) was stirred for 5 minutes at room temperature under nitrogen atmosphere. Then, tetrakis(triphenylphosphine)palladium(0) (78 mg, 0.07 mmol) was added at room temperature and the resulting light yellow solution was heated to 80° C. and stirred for 5 minutes. At this period, a solution of phenylboronic acid (99 mg, 0.82 mmol) in ethanol (5 mL) was added followed by a solution of sodium carbonate (86 mg, 0.82 mmol) in water (0.5 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 (30 mL). The two layers were separated and the aqueous layer was extracted with ethyl acetate (2×20 mL) and the combined organic extracts were washed with water (100 mL) and brine solution (100 mL). The organic layer was dried over anhydrous magnesium sulfate and filtration of the drying agent and removal of the solvent in vacuo gave the colored residue which was purified by using an ISCO 80 column, eluting with 0-30% ethyl acetate in hexanes to afford 4-[3-{6-[5-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-biphenyl-3-yloxy]-hexyl}-(2-(2-ethoxycarbonyl-ethyl)-phenoxy)-butyric acid ethyl ester (85 mg, 45%) as a light brown oil: ES(+)-HRMS m/e calculated for C43H50O8 (M+Na)+ 717.3398, found 717.3405.

Workup

  1. waitAt this period
  2. stirringThe resulting light yellow suspension was stirred for 24 h
  3. temperatureat reflux
  4. temperatureThen, the reaction mixture was cooled to room temperature
  5. customThe two layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL)
  7. washthe combined organic extracts were washed with water (100 mL) and brine solution (100 mL)
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate and filtration of the drying agent and removal of the solvent in vacuo
  9. customgave the colored residue which
  10. customwas purified
  11. washeluting with 0-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-714d55dfdf214bb098039d1246a66804
Source dataset
uspto-grants-2012_01
Patent number
US08093385B2

Reaction notes

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