Chloroacetonitrile → 3-Amino-5-tert-butylthiophene-2-carbonitrile

HRID 1529821Notes

Reaction equation

HRID 1529821 reaction equation
[S-2:1].[Na+].[Na+].Cl[C:5]([C:9]([CH3:12])([CH3:11])[CH3:10])=[CH:6][C:7]#[N:8].Cl[CH2:14][C:15]#[N:16].C[O-].[Na+]>CN(C=O)C.CO.O>[C:9]([C:5]1[S:1][C:14]([C:15]#[N:16])=[C:7]([NH2:8])[CH:6]=1)([CH3:12])([CH3:11])[CH3:10]

Participants

8

Reactant 4

HCID 7856ChloroacetonitrileHCID 14804Sodium SulfideHCID 27356613-Chloro-4,4-dimethylpent-2-enenitrileHCID 10942334Sodium Methoxide

Product 1

HCID 28084153-Amino-5-tert-butylthiophene-2-carbonitrileYield 65%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
75 °C

Procedure

To a suspension of sodium sulfide (3.26 g, 41.8 mmol) in DMF (42 mL) was added a solution of 3-chloro-4,4-dimethylpent-2-enenitrile (6.0 g, 41.8 mmol, Ohta, H.; Ishizaka, T.; Tatsuzuki, M.; Yoshinaga, M.; Iida, I.; Yamaguchi, T.; Tomishima, Y.; Futaki, N.; Toda, Y.; Saito, S. Bioorg. Med. Chem., 2008, 16, 1111-1124) in DMF (21 mL) at rt for 5 min and stirred the mixture at 70-80° C. for 2 h. Then chloroacetonitrile (5.3 mL, 83.6 mmol) was added dropwise to the reaction mixture and again stirred at 70-80° C. for 2 h. Then, a solution of sodium methoxide (2.26 g, 41.8 mmol) in dry methanol (42 mL) was added dropwise and stirring was continued for 2 h at the same temperature. The mixture was allowed to rt and poured into cold water and stirred for 30 min. The solution was extracted with chloroform (3×100 mL) and the combined chloroform layer was washed with water, brine and dried over sodium sulfate. The solution was filtered and evaporated the solvent. The residue was chromatographed over silica gel column using hexane-EtOAc (90:10) as eluent to give the product as a pale brown color solid (4.9 g, 65%), mp 118-122° C. 1H NMR (400 MHz, CDCl3): δ 6.32 (1H, s), 4.37 (2H, br s), 1.33 (9H, s); LC-MS (negative ion mode): m/z 179 (M−H)−.

Workup

  1. stirringagain stirred at 70-80° C. for 2 h
  2. stirringstirring
  3. waitwas continued for 2 h at the same temperature
  4. customwas allowed to rt
  5. stirringstirred for 30 min
  6. extractionThe solution was extracted with chloroform (3×100 mL)
  7. washthe combined chloroform layer was washed with water, brine
  8. dry with materialdried over sodium sulfate
  9. filtrationThe solution was filtered
  10. customevaporated the solvent
  11. customThe residue was chromatographed over silica gel column

Sources & evidence

ORD record
ord-c67f254bd4db4c49adfe23650435c3d0
Source dataset
uspto-grants-2015_07
Patent number
US09090633B2

Reaction notes

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