Dimethylformamide → N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-3-formylthiophene-2-carboxamide

HRID 886756Notes

Reaction equation

HRID 886756 reaction equation
[C:1]([NH:5][C:6]([C:8]1[S:9][C:10]([C:13]2[CH:18]=[C:17]([C:19](=[O:24])[NH:20][CH:21]3[CH2:23][CH2:22]3)[CH:16]=[CH:15][C:14]=2[CH3:25])=[CH:11][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C[O:29][CH2:28]C1.C([Li])CCC.CN(C=O)C>CCOC(C)=O>[C:1]([NH:5][C:6]([C:8]1[S:9][C:10]([C:13]2[CH:18]=[C:17]([C:19](=[O:24])[NH:20][CH:21]3[CH2:23][CH2:22]3)[CH:16]=[CH:15][C:14]=2[CH3:25])=[CH:11][C:12]=1[CH:28]=[O:29])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 68559715N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamideHCID 178418339Butyllithium

Product 1

HCID 86618192N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-3-formylthiophene-2-carboxamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

In 150 mL round-bottom flask equipped with a stir bar, under N2, was added N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide (1.2 g, 3.4 mmol) followed by anhydrous THF (100 mL). The solution was cooled down to −78° C. and butyllithium, (2.2 ml, 30 mmol) was added dropwise over 5 min. The mixture was stirred at −78° C. for 0.5 hrs and was added DMF (0.780 ml, 10 mmol). The mixture was stirred at −78° C. for 0.5 hr, quenched with saturated solution of NH4Cl and then allowed to warm up to room temperature. The reaction then diluted with EtOAc (100 ml) and the layers were separated and the aqueous layer was extracted with EtOAc (3×50 ml) and the combined organic solution was washed with brine, water and dried over MgSO4. The organic solutions were evaporated under reduced pressure and the crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 5% to 95% MeOH in DCM to provide N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-3-formylthiophene-2-carboxamide (1.01 g). MS (ES+): 385 (M+H)+

Workup

  1. customIn 150 mL round-bottom flask equipped with a stir bar, under N2
  2. stirringThe mixture was stirred at −78° C. for 0.5 hr
  3. customquenched with saturated solution of NH4Cl
  4. temperatureto warm up to room temperature
  5. customThe reaction
  6. customthe layers were separated
  7. extractionthe aqueous layer was extracted with EtOAc (3×50 ml)
  8. washthe combined organic solution was washed with brine, water
  9. dry with materialdried over MgSO4
  10. customThe organic solutions were evaporated under reduced pressure
  11. customchromatographed through a Redi-Sep pre-packed silica gel column (40 g)
  12. washeluting with a gradient of 5% to 95% MeOH in DCM

Sources & evidence

ORD record
ord-f9cda4b697404762a767ad0ffad09fc7
Source dataset
uspto-grants-2012_08
Patent number
US08247409B2

Reaction notes

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