Sodium Carbonate → 4-[3-[6-(3-Benzo[1,3]dioxol-5-yl-5-methanesulfonyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester

HRID 418080Notes

Reaction equation

HRID 418080 reaction equation
[CH2:1]([O:3][C:4](=[O:40])[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]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:25]=[C:24](I)[CH:23]=2)[C:10]=1[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH3:2].[C:41](=[O:44])([O-])[O-:42].[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:40])[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]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:25]=[C:24]([C:9]3[CH:14]=[CH:13][C:12]4[O:42][CH2:41][O:44][C:11]=4[CH:10]=3)[CH:23]=2)[C:10]=1[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH3:2]

Participants

8

Reactant 2

HCID 10340Sodium CarbonateHCID 578630374-{2-(2-Ethoxycarbonyl-ethyl)-3-[6-(3-iodo-5-methanesulfonyl-phenoxy)-hexyl]-phenoxy}-butyric Acid Ethyl Ester

Product 1

HCID 578630894-[3-[6-(3-Benzo[1,3]dioxol-5-yl-5-methanesulfonyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl esterYield 172.5%

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-{2-(2-ethoxycarbonyl-ethyl)-3-[6-(3-iodo-5-methanesulfonyl-phenoxy)-hexyl]-phenoxy}-butyric acid ethyl ester (1.14 g, 1.65 mmol) in dimethoxyethane (15 mL) was stirred for 5 minutes at room temperature under nitrogen atmosphere. Then, tetrakis(triphenylphosphine)palladium(0) (386 mg, 0.33 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 3,4-(methylenedioxyphenyl)boronic acid (566 g, 3.3 mmol) in ethanol (16 mL) was added followed by a solution of sodium carbonate (351 mg, 3.3 mmol) in water (1.0 mL). The resulting light yellow suspension was stirred for 15 h at reflux. Then, the reaction mixture was cooled to room temperature and diluted with water (50 mL) and ethyl acetate (50 mL). The two layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). 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 under reduced pressure gave the colored residue which was purified by using an ISCO 80 g column, eluting with 0-20% ethyl acetate in hexanes to afford 4-[3-[6-(3-benzo[1,3]dioxol-5-yl-5-methanesulfonyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (972 mg, 86%) as a light brown viscous oil: ES(+)-HRMS m/e calcd for C37H46O10S (M+Na)+ 705.2704, found 705.2703.

Workup

  1. waitAt this period
  2. stirringThe resulting light yellow suspension was stirred for 15 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 (2×50 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 under reduced pressure
  9. customgave the colored residue which
  10. customwas purified
  11. washeluting with 0-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-cbbfcb093c604c709e1317d1a1131cf2
Source dataset
uspto-grants-2012_01
Patent number
US08093253B2

Reaction notes

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