Triethylamine → 6-Chloro-N-methoxy-N-methylnicotinamide

HRID 626271Notes

Reaction equation

HRID 626271 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[CH:10][N:9]=1.Cl.[CH3:18][NH:19][O:20][CH3:21].C(N(CC)CC)C>O1CCCC1.ClCCl>[Cl:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([N:19]([O:20][CH3:21])[CH3:18])=[O:13])=[CH:10][N:9]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 792226-Chloronicotinic acidHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

Product 1

HCID 114355976-Chloro-N-methoxy-N-methylnicotinamideYield 73.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Oxalyl chloride 12.1 g (95.2 mmol) was added dropwise to a solution of 6-chloronicotinic acid 10.0 g (63.5 mmol) in 100 mL tetrahydrofuran. The reaction mixture was stirred at room temperature for 1 h, and then concentrated in vacuo to give a residue. The residue was dissolved in 50 mL dichloromethane to give a solution, which was added to a solution of N,O-dimethylhydroxylamine hydrochloride (12.4 g, 126.9 mmol) and triethylamine (25.7 g, 253.9 mmol) in 100 mL dichloromethane, stirred at room temperature for another 1 h, concentrated, and purified by column chromatography to afford the desired product as a colorless oil (9.4 g, 73.8%).

Workup

  1. concentrationconcentrated in vacuo
  2. customto give a residue
  3. customto give a solution, which
  4. stirringstirred at room temperature for another 1 h
  5. concentrationconcentrated
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-8d09a61ee9114f1a9418e93ea946542a
Source dataset
uspto-grants-2016_04
Patent number
US09309211B2

Reaction notes

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