Butyl iodide → Methyl 3-(butylamino)-5-(pyridin-4-yl)thiophene-2-carboxylate

HRID 2363951Notes

Reaction equation

HRID 2363951 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][CH2:21][CH2:22][CH3:23].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])[CH2:21][CH2:22][CH3:23]

Participants

9

Reactant 4

HCID 10962Butyl iodideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 43155531Methyl 3-amino-5-(pyridin-4-yl)thiophene-2-carboxylate

Product 1

HCID 66743415Methyl 3-(butylamino)-5-(pyridin-4-yl)thiophene-2-carboxylateYield 32%

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, 1-iodobutane (0.626 mL, 5.50 mmol) was added and stirring was continued for 5 h. The mixture was poured into water (60 mL) and sat. aqueous sodium hydrogen carbonate (60 mL). Ethyl acetate (100 mL) and THF (33 mL) were added to the mixture for extraction, and the insoluble precipitate was filtered off. 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 (0.460 g, 32%) as a yellow oil:

Workup

  1. waitwas continued for 5 h
  2. filtrationthe insoluble precipitate was filtered off
  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-ada874a2ba0e430a8046584309a3b276
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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