Hydrochloric Acid → Methyl 4-{[cyclohexyl(2-ethyl-5-formylthiophen-3-yl)methyl]amino}benzoate

HRID 1877258Notes

Reaction equation

HRID 1877258 reaction equation
Cl[CH:2]([CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:3]1[CH:4]=[C:5]([CH:10]2[O:14]CCO2)[S:6][C:7]=1[CH2:8][CH3:9].[NH2:21][C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=1.[I-].[Na+].Cl>O1CCCC1.O.CN(C)C(=O)C>[CH:15]1([CH:2]([NH:21][C:22]2[CH:23]=[CH:24][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:30][CH:31]=2)[C:3]2[CH:4]=[C:5]([CH:10]=[O:14])[S:6][C:7]=2[CH2:8][CH3:9])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 12082Methyl 4-aminobenzoateHCID 685143042-{4-[Chloro(cyclohexyl)methyl]-5-ethylthiophen-2-yl}-1,3-dioxolane

Product 1

HCID 86646397Methyl 4-{[cyclohexyl(2-ethyl-5-formylthiophen-3-yl)methyl]amino}benzoateYield 54.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 2-{4-[chloro(cyclohexyl)methyl]-5-ethylthiophen-2-yl}-1,3-dioxolane (3.08 g) synthesized above, methyl 4-aminobenzoate (2.96 g), sodium iodide (2.98 g) and N,N-dimethylacetamide (60 mL) sodium carbonate (2.08 g) was added, and the mixture was stirred overnight at 100° C. under an argon atmosphere. Water 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 (30% ethyl acetate/hexane) to give a yellow oil. To a solution of the obtained oil in tetrahydrofuran (40 mL) was added 1N hydrochloric acid (10 mL), and the mixture was stirred at room temperature for 1 hr. Tetrahydrofuran was evaporated using evaporator, 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 (40% ethyl acetate/hexane) to give the title compound (2.05 g, 54%) as a yellow solid.

Workup

  1. additionwas added
  2. customto quench
  3. customthe reaction
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (30% ethyl acetate/hexane)
  9. customto give a yellow oil
  10. stirringthe mixture was stirred at room temperature for 1 hr
  11. customTetrahydrofuran was evaporated
  12. customevaporator
  13. extractionthe mixture was extracted with ethyl acetate
  14. washThe extract was washed with saturated brine
  15. dry with materialdried over magnesium sulfate
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified by silica gel column chromatography (40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-8e66bf3891d14783b87fbceec6277897
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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