Sulfuric Acid → 6-Morpholin-4-yl-4-o-tolyl-nicotinamide

HRID 131112Notes

Reaction equation

HRID 131112 reaction equation
[C:1]([C:3]1[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[N:7][CH:8]=1)#[N:2].C1(C)C=CC=CC=1.S(=O)(=O)(O)[OH:30].[OH-].[Na+]>O>[CH3:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[C:4]1[CH:5]=[C:6]([N:9]2[CH2:10][CH2:11][O:12][CH2:13][CH2:14]2)[N:7]=[CH:8][C:3]=1[C:1]([NH2:2])=[O:30]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 1140TolueneHCID 14798Sodium HydroxideHCID 112197073-Pyridinecarbonitrile, 4-(2-methylphenyl)-6-(4-morpholinyl)-

Product 1

HCID 111622966-Morpholin-4-yl-4-o-tolyl-nicotinamideYield 101.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 5-cyano-4-(2-methylphenyl)-2-(4-morpholinyl)pyridine (17.71 g), 18 mL of toluene, and 17.0 mL (33.1 g, 319 mmol) of concentrated sulfuric acid was heated at 70° C. for 12 hours, cooled to room temperature, and quenched by addition of 100 mL of cold H2O. Ethyl acetate (100 mL) was added followed by a solution of 25.5 g (638 mmol) of sodium hydroxide in 50 mL of H2O. The aqueous layer was separated and extracted three times with 50 mL of ethyl acetate. The organic layers were combined and concentrated to afford 19.14 g of 4-(2-methylphenyl)-6-(4-morpholinyl)-3-pyridinecarboxamide as a colorless solid (LC assay 87.7 wt %) (yield 94.9–97%).

Workup

  1. temperaturecooled to room temperature
  2. customquenched by addition of 100 mL of cold H2O
  3. additionEthyl acetate (100 mL) was added
  4. customThe aqueous layer was separated
  5. extractionextracted three times with 50 mL of ethyl acetate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-155053cb5e13428ca644d93cbfe91b2a
Source dataset
uspto-grants-2008_06
Patent number
US07384939B2

Reaction notes

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