4-Methylmorpholine → (S)-tert-Butyl 2-(4-(2-phenyl-2H-1,2,3-triazole-4-carboxamido)phenyl)morpholine-4-carboxylate

HRID 1482904Notes

Reaction equation

HRID 1482904 reaction equation
[C:1]1([N:7]2[N:11]=[C:10]([C:12]([OH:14])=O)[CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([C@@H:22]2[O:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23]2)=[CH:18][CH:17]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CCOCC.O.CN(C=O)C>[C:1]1([N:7]2[N:11]=[C:10]([C:12]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([C@@H:22]4[O:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23]4)=[CH:18][CH:17]=3)=[O:14])[CH:9]=[N:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 7622772-phenyl-2H-1,2,3-triazole-4-carboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66705988(S)-Tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate

Product 1

HCID 90048137(S)-tert-Butyl 2-(4-(2-phenyl-2H-1,2,3-triazole-4-carboxamido)phenyl)morpholine-4-carboxylateYield 27.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

In a 25 mL round-bottomed flask, 2-phenyl-2H-1,2,3-triazole-4-carboxylic acid (CAS 13306-99-5) (59.8 mg, 316 μmol, Eq: 1.1), (S)-tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate (80 mg, 287 μmol, Eq: 1.00), N-methylmorpholine (87.2 mg, 94.8 μl, 862 μmol, Eq: 3) and HBTU (164 mg, 431 μmol, Eq: 1.5) were combined with DMF (2 ml) to give a yellow solution. The reaction mixture was stirred overnight at 60° C. The mixture was poured into water (10 ml) and extracted twice with EtOAc. The organic layers were washed with NaHCO3, brine, dried over MgSO4, filtered and concentrated in vacuo to give a brown crude mixture. This mixture was diluted with ether, stirred for 15 minutes and the suspension was filtered. The resulting solid was washed several times with ether to afford the desired compound as a light-yellow solid (35 mg, 27.1%).

Workup

  1. customto give a yellow solution
  2. extractionextracted twice with EtOAc
  3. washThe organic layers were washed with NaHCO3, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a brown crude mixture
  8. stirringstirred for 15 minutes
  9. filtrationthe suspension was filtered
  10. washThe resulting solid was washed several times with ether

Sources & evidence

ORD record
ord-f3bdffebc9aa408cb979d46806fc47eb
Source dataset
uspto-grants-2016_08
Patent number
US09416127B2

Reaction notes

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