4-Methylmorpholine → (-)-methyl(S)-2-[(2-amino-3-nitrobenzoyl)amino]propanoate

HRID 1491623

Reaction equation

HRID 1491623 reaction equation
[NH2:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[OH2:14].ON1[C:20]2C=CC=[N:24][C:19]=2[CH:18]=N1.CN1C[CH2:30][O:29]CC1>O1CCCC1>[NH2:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:24][C@@H:19]([CH3:18])[C:20]([O:29][CH3:30])=[O:14])=[O:6]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 2196332-Amino-3-nitrobenzoic acidHCID 701049091-hydroxy-1H-1,2,4-benzotriazole monohydrate

Product 1

HCID 14879834(-)-methyl(S)-2-[(2-amino-3-nitrobenzoyl)amino]propanoateYield 97.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred and cooled (-12° C.) mixture of 9.10 parts of 2-amino-3-nitrobenzoic acid, 6.95 parts of methyl L-α-alanine monohydrochloride, 13.50 parts of 1-hydroxy-1H-1,2,4-benzotriazole monohydrate and 178 parts of tetrahydrofuran there were added portionwise 5.05 parts of N-methylmorpholine and, after 5 min, 10.3 parts of N,N'-methanetetraylbis[cyclohexanamine] under an argon atmosphere. Stirring was continued for 51/2 hours at -12° C. and for 15 hours at room temperature. After cooling to 0° C. for 1/2 hour, the reaction mixture was filtered and the filtrate was evaporated. The residue was partitioned between ethyl acetate and a saturated sodium hydrogen carbonate solution. The organic layer was separated, washed with NaHCO3 (sat.), dried, filtered and evaporated. The residue was triturated with hexane. The product was filtered off and dried, yielding 13.08 parts (97.9%) of (-)-methyl (S)-2-[(2-amino-3-nitrobenzoyl)amino]propanoate; mp. 132.9° C. (interm. 24).

Workup

  1. temperaturecooled
  2. stirringStirring
  3. custom2 hours
  4. customat -12° C.
  5. waitfor 15 hours at room temperature
  6. filtrationthe reaction mixture was filtered
  7. customthe filtrate was evaporated
  8. customThe residue was partitioned between ethyl acetate
  9. customThe organic layer was separated
  10. washwashed with NaHCO3 (sat.)
  11. customdried
  12. filtrationfiltered
  13. customevaporated
  14. customThe residue was triturated with hexane
  15. filtrationThe product was filtered off
  16. customdried

Sources & evidence

ORD record
ord-bb1c76f9d7e444c5bbcb5c9b9a92608a
Source dataset
uspto-grants-1994_12
Patent number
US05371079

Linked notes

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