Nitrogen → 3-(2,4-Dichloro-benzylamino)-5-phenyl-thiophene-2-carboxylic acid methyl ester

HRID 1015620

Reaction equation

HRID 1015620 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[S:8][C:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:10][C:11]=1[NH2:12])=[O:6].N#N.[Cl:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[CH2:29]Cl>CN(C)C=O>[CH3:3][O:4][C:5]([C:7]1[S:8][C:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:10][C:11]=1[NH:12][CH2:29][C:23]1[CH:24]=[CH:25][C:26]([Cl:28])=[CH:27][C:22]=1[Cl:21])=[O:6]

Participants

6

Reactant 4

HCID 947NitrogenHCID 72122,4-Dichlorobenzyl chlorideHCID 24758Sodium hydrideHCID 700562Methyl 3-amino-5-phenylthiophene-2-carboxylate

Product 1

HCID 207757543-(2,4-Dichloro-benzylamino)-5-phenyl-thiophene-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% dispersion in oil, 180 mg, 4,72 mmol) was added to an ice-cold solution of 3-Amino-5-phenyl-thiophene-2-carboxylic acid methyl ester (1000 mg, 4,29 mmol) in 25 ml of dimethylformamide in an atmosphere of N2. After 5 min, 2,4-dichloro-1-chloromethyl-benzene (755 mg, 3,86 mmol) was added to the solution and then the reaction mixture was stirred for 30 min at 0° C. and 30 min at room temperature. The mixture was partitioned between ether (20 mL) and water (20 mL) and the organic layer was separated. The aqueous phase was washed twice with ether (2×20 mL) and the combined ether layer was dried (MgSO4) and concentrated. The residue obtained was then purified by precipitation. The crude product was taken in 25 ml of ethyl acetate, a yellow precipitate came out which was filtered to obtain 3-(2,4-Dichloro-benzylamino)-5-phenyl-thiophene-2-carboxylic acid methyl ester, 835 mg (55%). 1H-NMR (DMSO, 400 MHz): 7.67 ppm (m, 2H, Haro); 7.44-7.35 ppm (m, 6H, Haro); 7.26 ppm (s, 1H, Haro); 4.63 ppm (d, 2H, N—CH2); 3.75 ppm (s, 3H, O—CH3)

Workup

  1. customThe mixture was partitioned between ether (20 mL) and water (20 mL)
  2. customthe organic layer was separated
  3. washThe aqueous phase was washed twice with ether (2×20 mL)
  4. dry with materialthe combined ether layer was dried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue obtained
  7. customwas then purified by precipitation
  8. filtrationwas filtered

Sources & evidence

ORD record
ord-65b53ab1a2b8493d92e4fc5a1c54452a
Source dataset
uspto-grants-2011_07
Patent number
US07985769B2

Linked notes

Loading…