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Sulfuric Acid → 2-Chloro-3-methylpyridine-4-carboxylic acid

HRID 2208879
Notes
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Reaction equation

HRID 2208879 reaction equation
[Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([C:9](N(C)C2C=CC=CC=2)=[O:10])[CH:5]=[CH:4][N:3]=1.[OH:19]S(O)(=O)=O.C([O-])([O-])=O.[Na+].[Na+]>O>[Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([C:9]([OH:10])=[O:19])[CH:5]=[CH:4][N:3]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 150757162-Chloro-N,3-dimethyl-N-phenylisonicotinamide

Product 1

HCID 150757212-Chloro-3-methylpyridine-4-carboxylic acidYield 54%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

2-chloro-N,3-dimethyl-N-phenylpyridine-4-carboxamide (2.2 g, 8.5 mmol) was treated with a mixture of concentrated H2SO4 (23.2 ml) and water (16.8 ml) and then heated to 130° C. for 46 hours. After which time, the reaction mixture was allowed to reach room temperature and poured onto ice (200 ml) and stirred until the ice had melted. The mixture was made alkaline (pH 8) by the addition of solid Na2CO3 (50.3 g) portionwise. The suspension was filtered and the filtrate acidified to pH 3 by the addition of 6M HCl (aq) (˜1.5 ml). The resulting solid was collected by filtration, washed with water (20 ml) and dried in-vacuo at 40° C. for 10 hours to give the title compound (779 mg, 54%) as a pink solid. LC-MS 100%, m/z=171.9, 173.9; 1H NMR (500 MHz, MeOD) δ ppm 8.30 (d, J=4.89 Hz, 1H) 7.64 (d, J=5.04 Hz, 1H) 2.58 (s, 3H).

Workup

  1. customto reach room temperature
  2. additionpoured onto ice (200 ml)
  3. filtrationThe suspension was filtered
  4. additionthe filtrate acidified to pH 3 by the addition of 6M HCl (aq) (˜1.5 ml)
  5. filtrationThe resulting solid was collected by filtration
  6. washwashed with water (20 ml)
  7. customdried in-vacuo at 40° C. for 10 hours

Sources & evidence

ORD record
ord-869f8efc23c44f1bb2383dedd51d2b3d
Source dataset
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09376422B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes