Triethylamine → N-methoxy-N,5-dimethylnicotinamide

HRID 1787502Notes

Reaction equation

HRID 1787502 reaction equation
[CH3:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7](O)=[O:8].O=S(Cl)Cl.Cl.[CH3:16][NH:17][O:18][CH3:19].C(N(CC)CC)C>ClCCl>[CH3:19][O:18][N:17]([CH3:16])[C:7](=[O:8])[C:6]1[CH:10]=[C:2]([CH3:1])[CH:3]=[N:4][CH:5]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 2562085-Methylnicotinic acid

Product 1

HCID 59108679N-methoxy-N,5-dimethylnicotinamideYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 5-methyl-nicotinic acid (1.8 g, 13.1 mmole) and SOCl2 (10 mL) was heated to 75° C. for three hours. The remaining SOCl2 was removed by vacuum distillation and the oily residue carefully redissolved in dichloromethane (16 mL). Then N,O-dimethylhydroxyl amine hydrochloride (1.4 g, 14.4 mmol) was added. The reaction mixture was purged with argon and triethylamine (5.11 mL, 36.7 mmol) was dropwise added at 0° C. It was stirred for 24 hours at room temperature. The mixture was diluted with dichloromethane, washed with NaOH 2N, brine, dried and concentrated to yield a brown oil which was purified by column chromatography (SiO2, n-Hex/EtOAc 1:1 to EtOAc) to afford the title compound (1.7 g, 71% yield) as a brownish oil.

Workup

  1. customThe remaining SOCl2 was removed by vacuum distillation
  2. dissolutionthe oily residue carefully redissolved in dichloromethane (16 mL)
  3. additionwas dropwise added at 0° C
  4. washwashed with NaOH 2N, brine
  5. customdried
  6. concentrationconcentrated
  7. customto yield a brown oil which
  8. customwas purified by column chromatography (SiO2, n-Hex/EtOAc 1:1 to EtOAc)

Sources & evidence

ORD record
ord-389a825e4b26465681065419ed8770fe
Source dataset
uspto-grants-2009_03
Patent number
US07511038B2

Reaction notes

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