N-Methylethylamine → 6-Chloro-2-(ethyl(methyl)amino)-4-methyl-pyridine-3-carboxylic acid ethylester

HRID 922040Notes

Reaction equation

HRID 922040 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](Cl)=[N:8][C:9]([Cl:13])=[CH:10][C:11]=1[CH3:12])=[O:5])[CH3:2].[CH3:15][NH:16][CH2:17][CH3:18].CCN(C(C)C)C(C)C.[OH-].[Na+]>CN1C(=O)CCC1.O.CCOC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([N:16]([CH2:17][CH3:18])[CH3:15])=[N:8][C:9]([Cl:13])=[CH:10][C:11]=1[CH3:12])=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 12219N-MethylethylamineHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 70700301Ethyl 2,6-dichloro-4-methylnicotinate

Product 1

HCID 866643246-Chloro-2-(ethyl(methyl)amino)-4-methyl-pyridine-3-carboxylic acid ethylesterYield 44.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 8.2 g (35.0 mmol) 2,6-dichloro-4-methyl-pyridine-3-carboxylic acid ethylester, 3.7 ml (43.8 mmol) N-methylethylamine and 8.9 ml (52.5 mmol) DIPEA in NMP (25 ml) was heated in the MW to 90° C. for 1 h. Then the solution was diluted with water, a 1M aq. NaOH sol. and EtOAc. The organic layer was separated, dried over MgSO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 9:1) provided 4.0 g (15.6 mmol, 44%) 6-chloro-2-(ethyl(methyl)amino)-4-methyl-pyridine-3-carboxylic acid ethylester.

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue by CC (hexane/EtOAc 9:1)

Sources & evidence

ORD record
ord-cc8cfacc8e7d4192bdd9b78a1f435133
Source dataset
uspto-grants-2016_03
Patent number
US09278103B2

Reaction notes

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