Hydrochloric Acid → HCID 66779008, compound

HRID 2091036Notes

Reaction equation

HRID 2091036 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]([F:13])=[CH:9][C:6]=2[C:7]=1[CH3:8].[NH2:20][C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27]C)=[O:26])=[CH:23][CH:22]=1.[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].Cl.[OH-].[Na+]>C(O)C.O1CCCC1.CN(C)C=O>[CH:14]1([CH:2]([NH:20][C:21]2[CH:30]=[CH:29][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=2)[C:3]2[O:4][C:5]3[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:6]=3[C:7]=2[CH3:8])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 12082Methyl 4-aminobenzoateHCID 14798Sodium HydroxideHCID 66777694HCID 66777694, compound

Product 1

HCID 66779008HCID 66779008, compoundYield 54.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-[chloro(cyclohexyl)methyl]-5-fluoro-3-methyl-1-benzofuran (1.44 g) synthesized in Example A37(3), methyl 4-aminobenzoate (776 mg), sodium iodide (1.54 g) and N,N-dimethylformamide (30 mL) was added sodium carbonate (1.09 g), and the mixture was stirred at 80° C. overnight. 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 (20% ethyl acetate/hexane) to give a yellow solid. To a mixture of the obtained solid, tetrahydrofuran (20 mL) and ethanol (20 mL) was added 1N aqueous sodium hydroxide solution (20 mL), and the mixture was stirred overnight with heating under reflux, and concentrated under reduced pressure. The residue was dissolved in water (40 mL), and 1N hydrochloric acid (20 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title object compound (1.06 g, 54%) 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 brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (20% ethyl acetate/hexane)
  8. customto give a yellow solid
  9. stirringthe mixture was stirred overnight
  10. temperaturewith heating
  11. temperatureunder reflux
  12. concentrationconcentrated under reduced pressure
  13. dissolutionThe residue was dissolved in water (40 mL)
  14. addition1N hydrochloric acid (20 mL) was added at 0° C
  15. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-cc2d30f1077d4b70a1c1c603c072a3c7
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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