Hydrochloric Acid → 6-Morpholinonicotinic Acid

HRID 353827Notes

Reaction equation

HRID 353827 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:18]=[CH:17][C:10]([C:11]([O:13]C(C)C)=[O:12])=[CH:9][N:8]=2)[CH2:3][CH2:2]1.Cl>[OH-].[Na+]>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:18]=[CH:17][C:10]([C:11]([OH:13])=[O:12])=[CH:9][N:8]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 23512677Propan-2-yl 6-(morpholin-4-yl)pyridine-3-carboxylate

Product 1

HCID 27764606-Morpholinonicotinic Acid

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
55 °C

Procedure

A solution of isopropyl 6-chloronicotinate (6.0 g, 0.03 mol) and morpholine (13 mL, 0.15 mol) in isopropyl alcohol (60 mL) was heated at reflux for 72 hours. The solution was allowed to cool to ambient temperature overnight. The resulting precipitate was isolated by filtration, washed with isopropyl alcohol and dried to provide isopropyl 6-morpholinonicotinate. The filtrate was diluted with water. The resulting precipitate was isolated by filtration, washed with water and dried to provide isopropyl 6-morpholinonicotinate. The combined yield was 8.3 g. The isopropyl 6-morpholinonicotinate was combined with 1 N sodium hydroxide (40 mL) and the resulting suspension was stirred at 50-60° C. until all of the solid had dissolved. The solution was stirred at ambient temperature overnight during which time a precipitate formed. This material was isolated by filtration and identified as starting material. The filtrate was neutralized with concentrated hydrochloric acid. The resulting precipitate was isolated by filtration, washed with water and dried to provide 3.3 g of crude product. This material was recrystallized from methanol/dichloromethane to provide 6-morpholinonicotinic acid as a solid, m.p. 259-261° C. Analysis: Calculated for C10H12N2O3: % C, 57.19; % H, 5.81; % N, 13.48. Found: % C, 57.50; % H, 5.71; % N, 13.53.

Workup

  1. dissolutionhad dissolved
  2. stirringThe solution was stirred at ambient temperature overnight during which time a precipitate
  3. customformed
  4. customThis material was isolated by filtration
  5. customThe resulting precipitate was isolated by filtration
  6. washwashed with water
  7. customdried
  8. customto provide 3.3 g of crude product
  9. customThis material was recrystallized from methanol/dichloromethane

Sources & evidence

ORD record
ord-c001775e593a411787af9f25afd835c6
Source dataset
uspto-grants-2004_06
Patent number
US06756382B2

Reaction notes

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