Morpholine → Propan-2-yl 6-(morpholin-4-yl)pyridine-3-carboxylate

HRID 1280488Notes

Reaction equation

HRID 1280488 reaction equation
Cl[C:2]1[CH:13]=[CH:12][C:5]([C:6]([O:8][CH:9]([CH3:11])[CH3:10])=[O:7])=[CH:4][N:3]=1.[NH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1>C(O)(C)C>[O:17]1[CH2:18][CH2:19][N:14]([C:2]2[CH:13]=[CH:12][C:5]([C:6]([O:8][CH:9]([CH3:11])[CH3:10])=[O:7])=[CH:4][N:3]=2)[CH2:15][CH2:16]1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 23512700Isopropyl 6-chloronicotinate

Product 1

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

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

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. temperatureat reflux for 72 hours
  2. customThe resulting precipitate was isolated by filtration
  3. washwashed with isopropyl alcohol
  4. customdried

Sources & evidence

ORD record
ord-10bf2ff1929045dda813186da5c0371e
Source dataset
uspto-grants-2002_09
Patent number
US06451810B1

Reaction notes

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