1,2-Dimethoxyethane → HCID 59496831, compound

HRID 416990Notes

Reaction equation

HRID 416990 reaction equation
[CH2:1]([O:3][C:4](=[O:39])[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]([O:28][CH2:29][CH3:30])[CH:25]=[C:24](Br)[CH:23]=2)[C:10]=1[CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH3:2].[C:40]1(B(O)O)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(COC)OC>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]([O:3][C:4](=[O:39])[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:23]=[C:24]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH:25]=[C:26]([O:28][CH2:29][CH3:30])[CH:27]=2)[C:10]=1[CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH3:2]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 59496797HCID 59496797, compound

Product 1

HCID 59496831HCID 59496831, compoundYield 84.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 4-[3-[6-(3-bromo-5-ethoxy-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (305 mg, 0.5 mmol), phenylboronic acid (125 mg, 1.0 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (55 mg, 0.075 mmol), and cesium carbonate (331 mg, 1.0 mmol) in a microwave tube was added dimethoxyethane (5.9 mL) under nitrogen atmosphere at room temperature. The resulting brown reaction mixture was heated to 120° C. in a microwave for 30 minutes. The reaction mixture was diluted with ethyl acetate (50 mL) and the undissolved residue was filtered off and washed with water (50 mL). Then, the two layers of filtrate were separated and the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic extracts were washed with water (50 mL) and brine solution (50 mL). The organic layer was dried over anhydrous magnesium sulfate and filtration of the drying agent and removal of the solvent under vacuum gave the colored residue which was purified by using an ISCO 40 column, eluting with 2-25% ethyl acetate in hexanes to obtain 4-[3-[6-(5-ethoxy-biphenyl-3-yloxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (255 mg, 84%) as a colorless viscous oil: ES(+)-LRMS m/e calcd for C37H48O7 (M+Na)+ 627.3292. found 627.3292.

Workup

  1. filtrationthe undissolved residue was filtered off
  2. washwashed with water (50 mL)
  3. customThen, the two layers of filtrate were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (20 mL)
  5. washThe combined organic extracts were washed with water (50 mL) and brine solution (50 mL)
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate and filtration of the drying agent and removal of the solvent under vacuum
  7. customgave the colored residue which
  8. customwas purified
  9. washeluting with 2-25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f462e84033e04b18a1fdc97c782e5ef5
Source dataset
uspto-grants-2012_01
Patent number
US08088936B2

Reaction notes

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