Water → 2-Chloro-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid ethyl ester

HRID 1753905Notes

Reaction equation

HRID 1753905 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([Cl:14])=[N:8][C:9](Cl)=[CH:10][C:11]=1[CH3:12])=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.O>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([Cl:14])=[N:8][C:9]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:10][C:11]=1[CH3:12])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 8083MorpholineHCID 11430Potassium CarbonateHCID 70700301Ethyl 2,6-dichloro-4-methylnicotinate

Product 1

HCID 866719032-Chloro-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid ethyl esterYield 29.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 2,6-dichloro-4-methyl-pyridine-3-carboxylic acid ethyl ester (29.7 g, 127 mmol), potassium carbonate (26.3 g, 190 mmol), and morpholine (13.3 g, 152 mmol) in dimethylformamide (350 ml) is stirred for 18 h at 95° C. After completion of the reaction, water is added and the mixture is extracted with diethyl ether (3×). The combined organic layers are washed with water (2×) and brine (1×), dried over magnesium sulphate and evaporated to dryness. The crude product is purified by flash chromatography (silica gel, 25% ethyl acetate/cyclohexane) to yield 2-chloro-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid ethyl ester (10.5 g, 36.9 mmol, 29%).

Workup

  1. additionis added
  2. extractionthe mixture is extracted with diethyl ether (3×)
  3. washThe combined organic layers are washed with water (2×) and brine (1×)
  4. dry with materialdried over magnesium sulphate
  5. customevaporated to dryness
  6. customThe crude product is purified by flash chromatography (silica gel, 25% ethyl acetate/cyclohexane)

Sources & evidence

ORD record
ord-7bee75c02659494aa47e91ee3c01ddef
Source dataset
uspto-grants-2015_10
Patent number
US09168259B2

Reaction notes

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