Hydrochloric Acid → HCID 68512089, compound

HRID 1877205Notes

Reaction equation

HRID 1877205 reaction equation
Cl[CH:2]([CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[C:3]1[CH:4]=[C:5]([C:10]2[CH2:11][CH2:12][S:13][CH2:14][CH:15]=2)[S:6][C:7]=1[CH2:8][CH3:9].[NH2:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29]C)=[O:28])=[CH:25][CH:24]=1.[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].Cl.[OH-].[Na+]>C(O)C.O1CCCC1.CN(C)C(=O)C>[CH:16]1([CH:2]([NH:22][C:23]2[CH:32]=[CH:31][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=2)[C:3]2[CH:4]=[C:5]([C:10]3[CH2:11][CH2:12][S:13][CH2:14][CH:15]=3)[S:6][C:7]=2[CH2:8][CH3:9])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

10

Reactant 6

HCID 313Hydrochloric Acid2×HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 12082Methyl 4-aminobenzoateHCID 14798Sodium HydroxideHCID 68514363HCID 68514363, compound

Product 1

HCID 68512089HCID 68512089, compoundYield 31.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-{4-[chloro(cyclohexyl)methyl]-5-ethylthiophen-2-yl}-3,6-dihydro-2H-thiopyran (1.37 g) synthesized above, methyl 4-aminobenzoate (1.15 g), sodium iodide (1.15 g) and N,N-dimethylacetamide (20 mL) was added sodium carbonate (810 mg), and the mixture was stirred overnight at 100° C. under an argon atmosphere. To the reaction mixture was added 1N hydrochloric acid 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 (ethyl acetate:hexane=3:17, volume ratio) to give a pale-brown solid. To a mixture of the obtained solid, tetrahydrofuran (10 mL) and ethanol (10 mL) was added 1N aqueous sodium hydroxide solution (10 mL), and the mixture was stirred overnight at 50° C. To the reaction mixture was added 1N hydrochloric acid (10 mL), 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 (ethyl acetate:hexane=1:3, volume ratio) to give the title compound (554 mg, 31%) as a brown 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 (ethyl acetate:hexane=3:17, volume ratio)
  8. customto give a pale-brown solid
  9. stirringthe mixture was stirred overnight at 50° C
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe extract was washed with saturated brine
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:3, volume ratio)

Sources & evidence

ORD record
ord-4ad9699795e147e798b14b6ead0e1b41
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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