Hydrochloric Acid → {6-Cyano-4'-[3-(propane-2-sulfonylamino)-thiophen-2-yl]-biphenyl-3-yloxy}-acetic acid ethyl ester

HRID 746791

Reaction equation

HRID 746791 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[N:14])=[C:9](Cl)[CH:8]=1)[CH3:2].CC1(C)C(C)(C)OB([C:25]2[CH:30]=[CH:29][C:28]([C:31]3[S:32][CH:33]=[CH:34][C:35]=3[NH:36][S:37]([CH:40]([CH3:42])[CH3:41])(=[O:39])=[O:38])=[CH:27][CH:26]=2)O1.C([O-])([O-])=O.[Na+].[Na+].Cl>O1CCOCC1>[CH2:1]([O:3][C:4](=[O:16])[CH2:5][O:6][C:7]1[CH:8]=[C:9]([C:25]2[CH:26]=[CH:27][C:28]([C:31]3[S:32][CH:33]=[CH:34][C:35]=3[NH:36][S:37]([CH:40]([CH3:42])[CH3:41])(=[O:38])=[O:39])=[CH:29][CH:30]=2)[C:10]([C:13]#[N:14])=[CH:11][CH:12]=1)[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 59747992Propane-2-sulfonic acid {2-[4-(4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl)-phenyl]-thiophen-3-yl}-amideHCID 69253333(3-Chloro-4-cyano-phenoxy)-acetic acid ethyl ester

Product 1

HCID 69254554{6-Cyano-4'-[3-(propane-2-sulfonylamino)-thiophen-2-yl]-biphenyl-3-yloxy}-acetic acid ethyl esterYield 84%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Heat (3-chloro-4-cyano-phenoxy)-acetic acid ethyl ester (120 mg, 0.50 mmol), propane-2-sulfonic acid {2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-thiophen-3-yl}-amide (204 mg, 0.50 mmol), 2 M aqueous Na2CO3 solution (0.75 mL) and Pd(PCy3)2Cl2(55.4 mg, 0.075 mmol) in 1,4-dioxane (3.0 mL) to 80° C. under nitrogen atmosphere for 20 h. Pour into 0.1 M HCl solution and adjust pH to 7, then extract with diethyl ether (3×50 mL) and dry the combined organic phases (MgSO4) and concentrate to furnish a crude mixture as a yellowish solid. Purification by flash chromatography (Silica gel-Hexane /diethyl ether 1:1) yields 201 mg, 0.42 mmol (83%) of {6-Cyano-4′-[3-(propane-2-sulfonylamino)-thiophen-2-yl]-biphenyl-3-yloxy}-acetic acid ethyl ester as a pale yellow solid.

Workup

  1. extractionextract with diethyl ether (3×50 mL)
  2. dry with materialdry the combined organic phases (MgSO4)
  3. concentrationconcentrate
  4. customto furnish a crude mixture as a yellowish solid
  5. customPurification by flash chromatography (Silica gel-Hexane /diethyl ether 1:1)

Sources & evidence

ORD record
ord-674b8a35928541ff94f2f28787d764b4
Source dataset
uspto-grants-2008_07
Patent number
US07393868B2

Linked notes

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