Iodoethane → Methyl 3-(ethylamino)-5-(pyridin-4-yl)thiophene-2-carboxylate

HRID 2363942Notes

Reaction equation

HRID 2363942 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14].[H-].[Na+].I[CH2:20][CH3:21].C(=O)([O-])O.[Na+]>CN(C=O)C.C1COCC1.C(OCC)(=O)C.O>[CH2:20]([NH:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=2)[S:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14])[CH3:21]

Participants

9

Reactant 4

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 43155531Methyl 3-amino-5-(pyridin-4-yl)thiophene-2-carboxylate

Product 1

HCID 66743314Methyl 3-(ethylamino)-5-(pyridin-4-yl)thiophene-2-carboxylateYield 48.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of methyl 3-amino-5-(pyridin-4-yl)thiophene-2-carboxylate (1.21 g, 5.00 mmol) in DMF (25 mL) was added sodium hydride (60%, 0.220 g, 5.50 mmol). After 10 min, iodoethane (0.44 mL, 5.5 mmol) was added and stirring was continued for 4 h. The mixture was poured into water (60 mL) and sat. aqueous sodium hydrogen carbonate (60 mL). Ethyl acetate (120 mL) and THF (60 mL) were added to the mixture for extraction and the insoluble precipitate was removed by filtration. The organic layer was washed with brine, dried over magnesium sulfate, filtrated and concentrated at reduced pressure. The obtained residue was purified by column chromatography (Combiflash, 40 g silica gel, hexanes to 30:70 hexanes/ethyl acetate) to afford the title compound (0.636 g, 48%) as an orange solid:

Workup

  1. waitwas continued for 4 h
  2. customthe insoluble precipitate was removed by filtration
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltrated
  6. concentrationconcentrated at reduced pressure
  7. customThe obtained residue was purified by column chromatography (Combiflash, 40 g silica gel, hexanes to 30:70 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-33068e6c7765493894a5a818b440b78d
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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