Triethylamine → 4-chloro-N-methoxy-N-methylbenzo[b]thiophene-2-carboxamide

HRID 2183642Notes

Reaction equation

HRID 2183642 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[C:16]2[CH:15]=[C:14]([C:17]([OH:19])=O)[S:13][C:12]=2[CH:11]=[CH:10][CH:9]=1.Cl.[CH3:21][NH:22][O:23][CH3:24].C(N(CC)CC)C>ClCCl.CN(C)C=O.O>[Cl:7][C:8]1[C:16]2[CH:15]=[C:14]([C:17]([N:22]([O:23][CH3:24])[CH3:21])=[O:19])[S:13][C:12]=2[CH:11]=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 38545164-Chlorobenzo(b)thiophene-2-carboxylic Acid

Product 1

HCID 224738924-chloro-N-methoxy-N-methylbenzo[b]thiophene-2-carboxamideYield 91.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (9.2 ml) was added dropwise at 0° C. to a stirred suspension of 4-chlorobenzo[b]thiophene-2-carboxylic acid (17.89 g) in dichloromethane (240 ml), then the mixture was allowed to warm to ambient temperature. Dimethylformamide (8 drops) was added and the mixture was stirred at ambient temperature for 4 hours. The dichloromethane was removed in vacuo and tetrahydrofuran (200 ml) and dichloromethane (50 ml) were added to the residue to give a solution. N,O-Dimethylhydroxylamine hydrochloride (9.03 g) and triethylamine (25 ml) were added and the mixture was stirred at ambient temperature for 18 hours. Water (50 ml) and triethylamine (10 ml) were added then the solution was stirred at ambient temperature for 1 hour and diluted with water (1000 ml). The product was extracted into dichloromethane (3×300 ml), the combined extracts were dried (MgSO4) and the solvents were removed in vacuo. The residue was purified by flash chromatography over silica using a 19:1 mixture of dichloromethane and methanol as eluant. Appropriate fractions were combined and the solvents removed in vacuo to leave 4-chloro-N-methoxy-N-methylbenzo[b]thiophene-2-carboxamide (19.7 g) as an off-white solid which was used without further purification.

Workup

  1. customThe dichloromethane was removed in vacuo and tetrahydrofuran (200 ml) and dichloromethane (50 ml)
  2. additionwere added to the residue
  3. customto give a solution
  4. stirringthe mixture was stirred at ambient temperature for 18 hours
  5. stirringthe solution was stirred at ambient temperature for 1 hour
  6. extractionThe product was extracted into dichloromethane (3×300 ml)
  7. dry with materialthe combined extracts were dried (MgSO4)
  8. customthe solvents were removed in vacuo
  9. customThe residue was purified by flash chromatography over silica using
  10. additiona 19:1 mixture of dichloromethane and methanol as eluant
  11. customthe solvents removed in vacuo

Sources & evidence

ORD record
ord-3129c1de4ded4e1bb783e0bcc1dcc20e
Source dataset
uspto-grants-2005_05
Patent number
US06900216B2

Reaction notes

Loading…