Water → 7-Chloro-2-[(N-methoxy-N-methylamino)carbonyl]-3-nitroindole

HRID 379912Notes

Reaction equation

HRID 379912 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([OH:13])=O)=[C:7]2[N+:14]([O-:16])=[O:15].Cl.[CH3:18][NH:19][O:20][CH3:21].N1C=CC=CC=1.O>S(Cl)(Cl)=O>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([N:19]([O:20][CH3:21])[CH3:18])=[O:13])=[C:7]2[N+:14]([O-:16])=[O:15]

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 183678907-Chloro-3-nitroindole-2-carboxylic acid

Product 1

HCID 183679817-Chloro-2-[(N-methoxy-N-methylamino)carbonyl]-3-nitroindoleYield 87.1%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 7-chloro-3-nitroindole-2-carboxylic acid (step 1, 400 mg, 1.7 mmol) in thionyl chloride (2 ml) was heated at 70° C. for 3 h, the mixture cooled and concentrated. The residue was dissolved in dichloromethane (20 ml). To the solution was added N,O-dimethylhydroxylamine hydrochloride (326 mg, 3.4 mmol) and pyridine (0.27 ml, 3.4 mmol). After stirring for 16 h, the mixture was poured into water (100 ml) and extracted with ethyl acetate (200 ml). The organic layer was washed with 2N aqueous HCl (100 ml), water (100 ml), saturated aqueous sodium bicabonate (100 ml), brine (100 ml), and dried (MgSO4). After removal of solvent, the residue was purified by flash column chromatography eluting with ethyl acetate/hexane (1:10˜1:1) to give 420 mg (87%) of the title compound. tlc: Rf=0.55 (25% ethyl acetate in hexanes)

Workup

  1. temperaturethe mixture cooled
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in dichloromethane (20 ml)
  4. extractionextracted with ethyl acetate (200 ml)
  5. washThe organic layer was washed with 2N aqueous HCl (100 ml), water (100 ml), saturated aqueous sodium bicabonate (100 ml), brine (100 ml)
  6. dry with materialdried (MgSO4)
  7. customAfter removal of solvent
  8. customthe residue was purified by flash column chromatography
  9. washeluting with ethyl acetate/hexane (1:10˜1:1)

Sources & evidence

ORD record
ord-a39ae49880714410acee24eb237665f6
Source dataset
uspto-grants-2001_10
Patent number
US06300363B1

Reaction notes

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