Triethylamine → 6-Chloro-N-methoxy-N-methylpyridine-2-carboxamide

HRID 1636756Notes

Reaction equation

HRID 1636756 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][CH:3]=1.Cl.[CH3:12][NH:13][O:14][CH3:15].CCN(CC)CC>S(Cl)(Cl)=O.C(Cl)Cl>[CH3:15][O:14][N:13]([CH3:12])[C:8]([C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([Cl:1])[N:7]=1)=[O:10]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 208126-Chloropicolinic acidHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

Product 1

HCID 579421936-Chloro-N-methoxy-N-methylpyridine-2-carboxamideYield 103%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 24386Thionyl ChlorideSolvent2×

Procedure

10 g of 6-chloro-pyridine-2-carboxylic acid are dissolved in 50 ml of thionyl chloride and heated under reflux for 3.5 h. The solution is cooled and freed from excess thionyl chloride under reduced pressure. The crude product is taken up in 60 ml of methylene chloride and treated with 7.22 g of N,O-dimethyl-hydroxylamine.hydrochloride 25 ml of NEt3 in 30 ml of CH2Cl2 are added while cooling with ice and the solution is stirred at RT for 1.5 h., the suspension is filtered and the filtrate is washed with dilute sodium hydroxide solution and saturated sodium chloride solution and dried. After concentration of the solution 13.12 g of 6-chloro-pyridine-2-carboxylic acid methoxy-methyl-amide are obtained as the crude product. 6.7 g of this amide in 40 ml of THF are added dropwise at -78° C. to a solution of 40 ml of n-BuLi (1.6M in hexane) and 15 g of 1,4-dibromobenzene in 140 ml of THF. The solution is stirred at -78° C. for 2 h. and at 0° C. for 1 h. and then treated with 60 ml of 2M HCl. The phases are separated, the inorganic phase is extracted with 50 ml of ether and the organic phases are washed with sat. NaHCO3 solution and saturated sodium chloride solution and dried. The crude product is purified over silica gel with ethyl acetate:hexane (6:1) and recrystallized from ethyl acetate/hexane. There are obtained 6.75 g of (4-bromo-phenyl)-(6-chloro-pyridin-3-yl)-methanone, m.p 127.4° C., MS: m/e 295 (M, 1Br).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 3.5 h
  3. temperatureThe solution is cooled
  4. additionare added
  5. temperaturewhile cooling with ice
  6. filtrationthe suspension is filtered
  7. washthe filtrate is washed with dilute sodium hydroxide solution and saturated sodium chloride solution
  8. customdried

Sources & evidence

ORD record
ord-f202573613b54a79b1c65b96e8eda3b3
Source dataset
uspto-grants-2000_03
Patent number
US06034275

Reaction notes

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