1,2-Dimethoxyethane → 4-(2-(2-Ethoxycarbonyl-ethyl)-3-{6-[3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-methanesulfonyl-phenoxy]-hexyl}-phenoxy)-butyric acid ethyl ester

HRID 418082Notes

Reaction equation

HRID 418082 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].[O:41]1[C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=2[O:44][CH2:43][CH:42]1B(O)O.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: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:49]3[CH:48]=[CH:47][C:46]4[O:41][CH2:42][CH2:43][O:44][C:45]=4[CH:50]=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 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 534228272,3-Dihydro-1,4-benzodioxin-2-ylboronic acidHCID 578630374-{2-(2-Ethoxycarbonyl-ethyl)-3-[6-(3-iodo-5-methanesulfonyl-phenoxy)-hexyl]-phenoxy}-butyric Acid Ethyl Ester

Product 1

HCID 578630814-(2-(2-Ethoxycarbonyl-ethyl)-3-{6-[3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-methanesulfonyl-phenoxy]-hexyl}-phenoxy)-butyric acid ethyl esterYield 51.3%

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

A mixture of 4-{2-(2-ethoxycarbonyl-ethyl)-3-[6-(3-iodo-5-methanesulfonyl-phenoxy)-hexyl]-phenoxy}-butyric acid ethyl ester (646 mg, 0.94 mmol), 1,4-benzodioxaneboronic acid (337 g, 1.87 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (103 mg, 0.14 mmol), and cesium carbonate (617 mg, 1.87 mmol) was added dimethoxyethane (15 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 of the reaction mixture indicated the absence of starting material. 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) 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 under reduced pressure gave the colored residue which was purified by using an ISCO 80 column, eluting with 5-25% ethyl acetate in hexanes to afford 4-(3-{6-[3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-methanesulfonyl-phenoxy]-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy)-butyric acid ethyl ester (336 mg, 51%) as a light brown viscous oil: ES(+)-LRMS m/e calcd for C38H48O10S (M+H)+ 697.3, found 697.23.

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 (2×50 mL)
  4. washthe combined organic extracts were washed with water (100 mL) and brine solution (100 mL)
  5. 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
  6. customgave the colored residue which
  7. customwas purified
  8. washeluting with 5-25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-80479255c75d4d698566b08dc90fd23d
Source dataset
uspto-grants-2012_01
Patent number
US08093253B2

Reaction notes

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