p-Bromophenoxyacetic acid → {4'-[3-(Propane-2-sulfonylamino)-thiophen-2-yl]-biphenyl-4-yloxy}-acetic acid

HRID 746787

Reaction equation

HRID 746787 reaction equation
I[C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][C:8]([OH:10])=[O:9])=[CH:4][CH:3]=1.BrC1C=CC(OCC(O)=O)=CC=1.CC1(C)C(C)(C)OB([C:33]2[CH:38]=[CH:37][C:36]([C:39]3[S:40][CH:41]=[CH:42][C:43]=3[NH:44][S:45]([CH:48]([CH3:50])[CH3:49])(=[O:47])=[O:46])=[CH:35][CH:34]=2)O1.[OH-].[Ba+2].[OH-]>CN(C=O)C.O.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].ClCCl.O>[CH3:50][CH:48]([S:45]([NH:44][C:43]1[CH:42]=[CH:41][S:40][C:39]=1[C:36]1[CH:37]=[CH:38][C:33]([C:2]2[CH:12]=[CH:11][C:5]([O:6][CH2:7][C:8]([OH:10])=[O:9])=[CH:4][CH:3]=2)=[CH:34][CH:35]=1)(=[O:46])=[O:47])[CH3:49]

Participants

9

Reactant 4

HCID 74657p-Bromophenoxyacetic acidHCID 746584-Iodophenoxyacetic acidHCID 6093286Barium hydroxideHCID 59747992Propane-2-sulfonic acid {2-[4-(4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl)-phenyl]-thiophen-3-yl}-amide

Product 1

HCID 69253225{4'-[3-(Propane-2-sulfonylamino)-thiophen-2-yl]-biphenyl-4-yloxy}-acetic acidYield 65%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Procedure

Heat a solution of (4-Iodo-phenoxy)-acetic acid or (4-bromo-phenoxy)-acetic acid (0.25 mmol), propane-2-sulfonic acid {2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-thiophen-3-yl}-amide (122 mg, 0.30 mmol), PdCl2(dppf)(41 mg, 0.05 mmol) and barium hydroxide (158 mg, 0.50 mmol) in DMF-H2O (v/v 4:1, 2.5 mL) to 80° C. under nitrogen atmosphere for 20 h. Pour into H2O (50 mL) and dichloromethane (50 mL), then extract with H2O (4×50 mL) and dry the combined organic phases (MgSO4). Concentrate to furnish a crude mixture as a yellowish solid. Purification by flash chromatography (Silica gel-Hexane/EtOAc) affords the title compound as a pale yellow solid (65-80% yield). MS (ES−):430.1 (M−1).

Workup

  1. extractionextract with H2O (4×50 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/EtOAc)

Sources & evidence

ORD record
ord-c9bc2a267f5f4f9f8e14a35b2bf89860
Source dataset
uspto-grants-2008_07
Patent number
US07393868B2

Linked notes

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