Pyridine → Methyl 3-(4-cyclohexylphenylsulfonamido)thiophene-2-carboxylate

HRID 1925745Notes

Reaction equation

HRID 1925745 reaction equation
[CH:1]1([C:7]2[CH:12]=[CH:11][C:10]([S:13](Cl)(=[O:15])=[O:14])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:17][C:18]1[CH:22]=[CH:21][S:20][C:19]=1[C:23]([O:25][CH3:26])=[O:24].N1C=CC=CC=1>ClCCl>[CH:1]1([C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:17][C:18]3[CH:22]=[CH:21][S:20][C:19]=3[C:23]([O:25][CH3:26])=[O:24])(=[O:15])=[O:14])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 89652Methyl 3-amino-2-thiophenecarboxylateHCID 43394424-Cyclohexylbenzene-1-sulfonyl chloride

Product 1

HCID 59180410Methyl 3-(4-cyclohexylphenylsulfonamido)thiophene-2-carboxylateYield 90.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-cyclohexylbenzene-1-sulfonyl chloride (0.45 g; 1.74 mmol) in dichloromethane (4.0 mL) at room temperature, methyl 3-aminothiophene-2-carboxylate (0.25 g; 1.6 mmol) was added followed by pyridine (0.25 g; 3.2 mmol) and then stirred at room temperature under a nitrogen atmosphere for 24 hours. The reaction mixture was concentrated under reduced pressure and then taken up in ethyl acetate (50 mL) and extracted with water. The aqueous layer separated and extracted with ethyl acetate (2×50 mL). The combined organic phases were successively washed with water and aqueous saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting crude residue was purified by automated silica gel column chromatography (Biotage®) eluting with ethyl acetate/hexanes (0 to 40% v/v over 900 mL gradient elution) to give the title product as an off-white solid (0.55 g).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionextracted with water
  3. customThe aqueous layer separated
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. washThe combined organic phases were successively washed with water and aqueous saturated sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting crude residue was purified by automated silica gel column chromatography (Biotage®)
  10. washeluting with ethyl acetate/hexanes (0 to 40% v/v over 900 mL gradient elution)

Sources & evidence

ORD record
ord-b189635347c34ad5a18f45d12f5d5f8e
Source dataset
uspto-grants-2012_05
Patent number
US08178699B2

Reaction notes

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