Hydrochloric Acid → 3-(2-(4-fluoro-1H-indol-2-yl)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-3-yl)propanoic acid

HRID 595745Notes

Reaction equation

HRID 595745 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]1[C:16]([CH2:17][CH2:18][C:19]([O:21]CC)=[O:20])=[CH:15][CH:14]=[C:13]([C:24]3[C:25]([N:44]([CH3:49])[S:45]([CH3:48])(=[O:47])=[O:46])=[CH:26][C:27]4[O:31][C:30]([C:32]5[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=5)=[C:29]([C:39](=[O:42])[NH:40][CH3:41])[C:28]=4[CH:43]=3)[N:12]=1)[NH:6]2.O.[OH-].[Li+].CO.Cl>C1COCC1.CCOC(C)=O.O>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]1[C:16]([CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[CH:15][CH:14]=[C:13]([C:24]3[C:25]([N:44]([CH3:49])[S:45]([CH3:48])(=[O:46])=[O:47])=[CH:26][C:27]4[O:31][C:30]([C:32]5[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=5)=[C:29]([C:39](=[O:42])[NH:40][CH3:41])[C:28]=4[CH:43]=3)[N:12]=1)[NH:6]2

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 168937Lithium hydroxide, monohydrateHCID 90333603ethyl 3-(2-(4-fluoro-1H-indol-2-yl)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-3-yl)propanoate

Product 1

HCID 903334323-(2-(4-fluoro-1H-indol-2-yl)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-3-yl)propanoic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of ethyl 3-(2-(4-fluoro-1H-indol-2-yl)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-3-yl)propanoate (91 mg, 0.133 mmol) and lithium hydroxide monohydrate (27.8 mg, 0.663 mmol) were suspended in THF (0.53 mL), MeOH (0.27 mL), and H2O (0.2 mL). The resultant mixture was stirred at ambient temperature overnight then cooled in an ice bath and acidified to pH 2 with 1 N HCl. The mixture was then diluted with EtOAc and H2O, separated into layers and the aqueous layer extracted with EtOAc (2×). The combined organic layers were washed with brine (4×) until last brine wash was pH 7 then were dried over MgSO4, filtered, and concentrated in vacuo. The resulting product was azeotroped from CH3CN (4×) and used as a tan solid without further purification. MS (M+H)+: 659.

Workup

  1. temperaturethen cooled in an ice bath
  2. customseparated into layers
  3. extractionthe aqueous layer extracted with EtOAc (2×)
  4. washThe combined organic layers were washed with brine (4×) until last brine
  5. washwash
  6. dry with materialthen were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting product was azeotroped from CH3CN (4×)
  10. customused as a tan solid without further purification

Sources & evidence

ORD record
ord-fe9730e97aa742f9ab63defaab1951ea
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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