Hydrochloric Acid → 3-{[(4-{[Cyclohexyl(3,5-dimethyl-1-benzofuran-2-yl)methyl]amino}phenyl)carbonyl]amino}propanoic acid

HRID 2091128Notes

Reaction equation

HRID 2091128 reaction equation
Cl[CH:2]([CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[C:3]1[O:4][C:5]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][C:6]=2[C:7]=1[CH3:8].[NH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([NH:29][CH2:30][CH2:31][C:32]([O:34]CC)=[O:33])=[O:28])=[CH:23][CH:22]=1.[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].Cl>C(O)C.O1CCCC1.CN(C)C=O>[CH:14]1([CH:2]([NH:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]([NH:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[O:28])=[CH:25][CH:26]=2)[C:3]2[O:4][C:5]3[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][C:6]=3[C:7]=2[CH3:8])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 12469762Ethyl 3-(4-aminobenzamido)propanoateHCID 667790612-[Chloro(cyclohexyl)methyl]-3,5-dimethyl-1-benzofuran

Product 1

HCID 686285753-{[(4-{[Cyclohexyl(3,5-dimethyl-1-benzofuran-2-yl)methyl]amino}phenyl)carbonyl]amino}propanoic acidYield 67.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-[chloro(cyclohexyl)methyl]-3,5-dimethyl-1-benzofuran (400 mg) synthesized above, ethyl 3-{[(4-aminophenyl)carbonyl]amino}propanoate (343 mg) synthesized in Example 1(2), sodium iodide (327 mg), sodium carbonate (231 mg) and N,N-dimethylformamide (10 mL) was stirred at 80° C. for 5 hr. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (45% ethyl acetate/hexane) to give a yellow oil. To a mixture of the obtained oil, tetrahydrofuran (5 mL) and ethanol (5 mL) 1N aqueous sodium hydroxide solution (2.00 mL) were added, and the mixture was stirred at room temperature for 2 hr, and concentrated under reduced pressure. The residue was dissolved in water (10 mL), and 1N hydrochloric acid (2.00 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title object compound (436 mg, 67%) as a white solid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (45% ethyl acetate/hexane)
  8. customto give a yellow oil
  9. additionwere added
  10. stirringthe mixture was stirred at room temperature for 2 hr
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe residue was dissolved in water (10 mL)
  13. addition1N hydrochloric acid (2.00 mL) was added at 0° C
  14. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-17b1775fefd2402bad2d7cb9247428be
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

Loading…