Hydrochloric Acid → HCID 66778519, compound

HRID 2091123Notes

Reaction equation

HRID 2091123 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH:10](Cl)[CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)=[C:7]([CH3:18])[C:6]=2[CH:19]=1.[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>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH:10]([NH:20][C:21]3[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]=3)[CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)=[C:7]([CH3:18])[C:6]=2[CH:19]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 12469762Ethyl 3-(4-aminobenzamido)propanoateHCID 66778915HCID 66778915, compound

Product 1

HCID 66778519HCID 66778519, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-chloro-2-[chloro(cyclohexyl)methyl]-3-methyl-1-benzofuran (270 mg) synthesized above, ethyl 3-{[(4-aminophenyl)carbonyl]amino}propanoate (215 mg) synthesized in Example 1(2), sodium iodide (204 mg), sodium carbonate (144 mg) and N,N-dimethylformamide (10 mL) was stirred overnight at 80° C. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (50% ethyl acetate/hexane) to give a pale-yellow oil. To a mixture of the obtained oil, tetrahydrofuran (5 mL) and ethanol (5 mL) 1N aqueous sodium hydroxide solution (1.00 mL) was added, and the mixture was stirred at room temperature for 2 hr, and the reaction mixture was concentrated under reduced pressure. The residue was dissolved in water (10 mL), and 1N hydrochloric acid (1.00 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title object compound (132 mg, 31%) as a yellow solid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (50% ethyl acetate/hexane)
  8. customto give a pale-yellow oil
  9. additionwas added
  10. stirringthe mixture was stirred at room temperature for 2 hr
  11. concentrationthe reaction mixture was concentrated under reduced pressure
  12. dissolutionThe residue was dissolved in water (10 mL)
  13. addition1N hydrochloric acid (1.00 mL) was added at 0° C
  14. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-ff575e05ba6d4051bb69a964d02b00ac
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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