Hydrochloric Acid → {5-Chloro-2'-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-4'-methylsulfanyl-biphenyl-3-yl}-acetic acid

HRID 563683Notes

Reaction equation

C([O:3][C:4](=[O:29])[CH2:5][C:6]1[CH:7]=[C:8]([C:13]2[CH:18]=[CH:17][C:16](F)=[CH:15][C:14]=2[CH2:20][N:21]([C:24]([CH:26]2[CH2:28][CH2:27]2)=[O:25])[CH2:22][CH3:23])[CH:9]=[C:10]([Cl:12])[CH:11]=1)C.[CH3:30][S-:31].[Na+].[F-].Cl>CN(C=O)C.O.CCOC(C)=O>[Cl:12][C:10]1[CH:11]=[C:6]([CH2:5][C:4]([OH:3])=[O:29])[CH:7]=[C:8]([C:13]2[CH:18]=[CH:17][C:16]([S:31][CH3:30])=[CH:15][C:14]=2[CH2:20][N:21]([C:24]([CH:26]2[CH2:28][CH2:27]2)=[O:25])[CH2:22][CH3:23])[CH:9]=1

Participants

Conditions

Temperature: 100 °C

Procedure

{5-Chloro-2′-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-4′-fluoro-biphenyl-3-yl}-acetic acid ethyl ester (0.118 g, 0.28 mmol) and sodium thiomethoxide (0.043 g, 0.62 mmol) were combined in DMF (2 mL) and stirred at 100° C. overnight. Analytical LCMS indicated that the fluoride hadn't been displaced, but the ethyl ester had hydrolyzed. Additional sodium thiomethoxide (0.040 g, 0.57 mmol) was added, and the reaction was stirred overnight at 100° C. Analytical LCMS indicated that the reaction was complete, so the mixture was acidified with 1N aqueous HCl (4 mL) and worked-up with EtOAc and H2O. The combined organic layers were dried, filtered, and concentrated, and the residue was purified by preparative HPLC to give the title compound. M+H is 418.

Workup

stirringthe reaction was stirred overnight at 100° C
customThe combined organic layers were dried
filtrationfiltered
concentrationconcentrated
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-dca22a66153d4d52a4ebaa2ef3d3715a
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067445B2

Reaction notes

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