Aniline → N-phenylmorpholine-2-carboxamide

HRID 2367293Notes

Reaction equation

HRID 2367293 reaction equation
CC(OC([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([OH:16])=O)[CH2:9]1)=O)(C)C.CCN=C=NCCCN(C)C.[CH:28]1[CH:29]=[CH:30][C:31]2N(O)N=[N:34][C:32]=2[CH:33]=1.NC1C=CC=CC=1>CN(C=O)C.CCOCC>[C:32]1([NH:34][C:14]([CH:10]2[O:11][CH2:12][CH2:13][NH:8][CH2:9]2)=[O:16])[CH:33]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

7

Reactant 4

HCID 6115AnilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27559654-((Tert-butoxy)carbonyl)morpholine-2-carboxylic acid

Product 1

HCID 20468530N-phenylmorpholine-2-carboxamideYield 135.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-{[(1,1-dimethylethyl)oxy]carbonyl}-2-morpholinecarboxylic acid (500 mg, 2.16 mmol) in dry DMF (2 mL) at 0° C. were added EDCI (456 mg, 2.38 mmol), HOBT (331 mg, 2.16 mmol) and aniline (0.22 mL, 2.38 mmol). The solution was stirred at room temperature overnight. The solvent was evaporated and the resulting residue was poured onto water and extracted with EtOAc (2×) and CH2Cl2 (2×). The combined organics were washed with brine and dried (MgSO4), filtered and evaporated. To this crude material dissolved in CH2Cl2/CH3OH (3 mL/0.3 mL) was added TFA (1.5 mL), and the reaction mixture was stirred at room temperature for 3 hours. The mixture was concentrated and dried in vacuo to afford a light brown oil. Et2O and hexanes were added and a precipitate crashed out. The mixture was sonicated and filtered to afford the title compound (604 mg). LC-MS (ES) m/z=207 [M+H]+.

Workup

  1. customThe solvent was evaporated
  2. additionthe resulting residue was poured onto water
  3. extractionextracted with EtOAc (2×) and CH2Cl2 (2×)
  4. washThe combined organics were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionTo this crude material dissolved in CH2Cl2/CH3OH (3 mL/0.3 mL)
  9. additionwas added TFA (1.5 mL)
  10. stirringthe reaction mixture was stirred at room temperature for 3 hours
  11. concentrationThe mixture was concentrated
  12. customdried in vacuo
  13. customto afford a light brown oil
  14. customThe mixture was sonicated
  15. filtrationfiltered

Sources & evidence

ORD record
ord-fb8c46c70f9b4520a1c12060433f3868
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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