4-Methylmorpholine → HCID 14555272, compound

HRID 1723482Notes

Reaction equation

HRID 1723482 reaction equation
[CH2:1]([NH:8][C:9](=[O:26])[C:10]1[CH:15]=[CH:14][CH:13]=[N:12][C:11]=1[O:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23](O)=[O:24])[CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:27][N:28]1CCOCC1.ClC(OCC(C)C)=O>C1COCC1>[CH2:1]([NH:8][C:9](=[O:26])[C:10]1[CH:15]=[CH:14][CH:13]=[N:12][C:11]=1[O:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23](=[O:24])[NH:28][CH3:27])[CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 14555270HCID 14555270, compound

Product 1

HCID 14555272HCID 14555272, compoundYield 60.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

N-Benzyl 2-(3-carboxyphenoxy)nicotinamide (1.00 gram, 2.87 mmol) is placed into a 100 ml 3-neck round bottom flask equipped with magnetic stir bar, thermometer, nitrogen inlet and a rubber septum. The flash is charged with 15 ml of THF and N-methylmorpholine (0.29 grams, 2.87 mmol) is added via syringe. The reaction is chilled to -10° C. and isobutyl chloroformate 0.39 grams, 2.87 mmol) added to the reaction via syringe while maintaining the temperature at less than 0° C. The reaction is stirred at -10° C. for 30 minutes. Monomethylamine gas is bubbled into the reaction via syringe while maintaining the temperature below 0° C. The reaction is allowed to slowly warm to room temperature. After stirring for 21/2hours, water (20 ml) is added to the reaction which is then extracted with ethyl acetate (2×100 ml). The organics are combined and washed with 2N sodium hydroxide (4×75 ml) and (1×100 ml) water. The organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield a paste. The crude product is purified by trituration with diethyl ether to yield 0.63 grams (60.6%) of the title product as a white solid.

Workup

  1. customequipped with magnetic stir bar
  2. additionis added via syringe
  3. temperaturewhile maintaining the temperature at less than 0° C
  4. customMonomethylamine gas is bubbled into the reaction via syringe
  5. temperaturewhile maintaining the temperature below 0° C
  6. temperatureto slowly warm to room temperature
  7. stirringAfter stirring for 21/2hours, water (20 ml)
  8. additionis added to the reaction which
  9. extractionis then extracted with ethyl acetate (2×100 ml)
  10. washwashed with 2N sodium hydroxide (4×75 ml) and (1×100 ml) water
  11. dry with materialThe organic layer is dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto yield a paste
  15. customThe crude product is purified by trituration with diethyl ether

Sources & evidence

ORD record
ord-01a3c246b17b424682652a28018efeff
Source dataset
uspto-grants-1989_08
Patent number
US04861891

Reaction notes

Loading…