1,2-Dimethoxyethane → 4-{2-(2-Ethoxycarbonyl-ethyl)-3-[6-(5-hydroxymethyl-4'-methanesulfonyl-biphenyl-3-yloxy)-hexyl]-phenoxy}-butyric acid ethyl ester

HRID 416967Notes

Reaction equation

HRID 416967 reaction equation
[CH2:1]([O:3][C:4](=[O:38])[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]([CH2:28][OH:29])[CH:25]=[C:24](Br)[CH:23]=2)[C:10]=1[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH3:2].[CH3:39][S:40]([C:43]1[CH:48]=[CH:47][C:46](B(O)O)=[CH:45][CH:44]=1)(=[O:42])=[O:41].C(=O)([O-])[O-].[Cs+].[Cs+].C(COC)OC>O.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:38])[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:46]3[CH:47]=[CH:48][C:43]([S:40]([CH3:39])(=[O:42])=[O:41])=[CH:44][CH:45]=3)[CH:25]=[C:26]([CH2:28][OH:29])[CH:27]=2)[C:10]=1[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH3:2]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 594968024-[3-[6-(3-Bromo-5-hydroxymethyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester

Product 1

HCID 594968084-{2-(2-Ethoxycarbonyl-ethyl)-3-[6-(5-hydroxymethyl-4'-methanesulfonyl-biphenyl-3-yloxy)-hexyl]-phenoxy}-butyric acid ethyl esterYield 55.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
96 °C

Procedure

To a mixture of 4-[3-[6-(3-bromo-5-hydroxymethyl-phenoxy)-hexyl]-2-(2-ethyoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (2.0 g, 3.34 mmol), 4-methanesulfonylphenylboronic acid (1.35 g, 6.74 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (369.8 mg, 0.51 mmol), and cesium carbonate (2.22 g, 6.74 mmol) was added dimethoxyethane (100 mL) at room temperature under nitrogen atmosphere. The resulting brown reaction mixture was heated to 96° C. and stirred for 15 h at which time the TLC analysis of the reaction mixture indicated the absence of starting material. Then, the reaction mixture was cooled to room temperature and diluted with water and ethyl acetate. The two layers were separated and the aqueous layer was extracted with ethyl acetate and the combined organic extracts were washed with water and brine solution. 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 120 g column to obtain 4-{2-(2-ethoxycarbonyl-ethyl)-3-[6-(5-hydroxymethyl-4′-methanesulfonyl-biphenyl-3-yloxy)-hexyl]-phenoxy}-butyric acid ethyl ester (1.23 g, 55%) as a light brown oil: ES(+)-HRMS m/e calcd for C37H48O9S (M+Na)+ 691.2911. found 691.2913.

Workup

  1. temperatureThen, the reaction mixture was cooled to room temperature
  2. customThe two layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washthe combined organic extracts were washed with water and brine solution
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate and filtration of the drying agent and removal of the solvent under vacuum
  6. customgave the colored residue which
  7. customwas purified

Sources & evidence

ORD record
ord-d5907cb048c84e6b971be5ffc4e454a2
Source dataset
uspto-grants-2012_01
Patent number
US08088936B2

Reaction notes

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