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

HRID 240885Notes

Reaction equation

HRID 240885 reaction equation
[Cl:1][C:2]1[C:10]2[CH:9]=[C:8]([C:11]([OH:13])=O)[S:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl.[CH3:15][NH:16][O:17][CH3:18].C1CCC(N=C=NC2CCCCC2)CC1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:1][C:2]1[C:10]2[CH:9]=[C:8]([C:11]([N:16]([O:17][CH3:18])[CH3:15])=[O:13])[S:7][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 38545164-Chlorobenzo(b)thiophene-2-carboxylic Acid

Product 1

HCID 224738924-chloro-N-methoxy-N-methylbenzo[b]thiophene-2-carboxamideYield 75.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Stir a mixture of 4-chlorobenzo[b]thiophene-2-carboxylic acid (0.94 g, 4.44 mmol), N,O-dimethylhydroxylamine hydrochloride (0.86 g, 8.87 mmol), DCC (1.1 g, 5.32 mmol) and DIEA (1.43 g, 1.9 mL, 11.08 mmol) in DCM (8 mL) at ambient temperature for 2 hours. Filter the reaction mixture and the filtrate is washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. Purify the residue by column chromatography on silica gel eluting with PE:EtOAc (5:1 to 3:1) to afford 4-chloro-N-methoxy-N-methylbenzo[b]thiophene-2-carboxamide as white solid (0.85 g, 75.2%). 1H NMR (400 MHz, CDCl3) δ 8.10-8.02 (m, 2H), 7.61-7.51 (m, 2H), 3.84-3.79 (s, 3H), 3.37-3.35 (s, 3H).

Workup

  1. filtrationFilter the reaction mixture
  2. washthe filtrate is washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under vacuum
  5. customPurify the residue by column chromatography on silica gel eluting with PE

Sources & evidence

ORD record
ord-76f607c461cf477c9c328aa49cefd277
Source dataset
uspto-grants-2014_02
Patent number
US08648081B2

Reaction notes

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