Sodium Hydroxide → 2-Cyclopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid

HRID 1753907Notes

Reaction equation

HRID 1753907 reaction equation
C([O:3][C:4]([C:6]1[C:7]([CH:19]2[CH2:21][CH2:20]2)=[N:8][C:9]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:10][C:11]=1[CH3:12])=[O:5])C.[OH-].[Na+]>CO.O1CCCC1>[CH:19]1([C:7]2[C:6]([C:4]([OH:5])=[O:3])=[C:11]([CH3:12])[CH:10]=[C:9]([N:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)[N:8]=2)[CH2:21][CH2:20]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 708168332-Cyclopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid ethyl ester

Product 1

HCID 672877532-Cyclopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acidYield 69%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of 2-cyclopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid ethyl ester (16.8 g, 57.8 mmol) in methanol-tetrahydrofuran (1:1) (90 ml) is treated for 3 days with a 2M aqueous solution of sodium hydroxide at reflux. The organic solvent is distilled off and the aqueous layer treated with 2M hydrochloric acid, and extracted with ethyl acetate. The combined organic layers are dried over magnesium sulphate and evaporated to dryness. The crude product is purified by flash chromatography (silica gel, 75% ethyl acetate/cyclohexane) to yield 2-cyclopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid (10.4 g, 39.6 mmol, 69%).

Workup

  1. temperatureat reflux
  2. distillationThe organic solvent is distilled off
  3. additionthe aqueous layer treated with 2M hydrochloric acid
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined organic layers are dried over magnesium sulphate
  6. customevaporated to dryness
  7. customThe crude product is purified by flash chromatography (silica gel, 75% ethyl acetate/cyclohexane)

Sources & evidence

ORD record
ord-318233f52fa744ad9a6e85af129487bd
Source dataset
uspto-grants-2015_10
Patent number
US09168259B2

Reaction notes

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