4-Methylmorpholine → (4-N-tert-butoxycarbonylpiperazinylmethyl-2-phenylbenzoyl)methionine methyl ester

HRID 325238Notes

Reaction equation

HRID 325238 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[C:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[C:17]([CH:21]=[CH:22][CH:23]=2)[C:18](O)=[O:19])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:31][C@H:32]([C:37]([O:39][CH3:40])=[O:38])[CH2:33][CH2:34][S:35][CH3:36].ON1C(=O)C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.CN1CCOCC1>CN(C=O)C.C(OCC)(=O)C.CCCCCC.C(OCC)(=O)C>[CH3:40][O:39][C:37](=[O:38])[C@H:32]([CH2:33][CH2:34][S:35][CH3:36])[NH:31][C:18](=[O:19])[C:17]1[CH:21]=[CH:22][CH:23]=[C:15]([CH2:14][N:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:13][CH2:12]2)[C:16]=1[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 11435579L-Methionine, methyl ester, hydrochlorideHCID 702294364-N-tert-butoxycarbonylpiperazinylmethyl-2-phenylbenzoic acid

Product 1

HCID 70226068(4-N-tert-butoxycarbonylpiperazinylmethyl-2-phenylbenzoyl)methionine methyl esterYield 48%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

A solution of the product of Example 290A (0.544 g, 1.37 mmol), L-methionine, methyl ester hydrochloride (0.553 g, 2.74 mmol), 3-hydroxy-1,2,3-benzotriazin-4(3H)-one (1.14 g, 6.85 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.34 g, 6.85 mmol), and N-methylmorpholine (0.980 g, 9.59 mmol) in DMF (14 nlL) was stirred at ambient temperature for 16 hours. The mixture was diluted with ethyl acetate and then extracted with a 2:1 mixture of H2O and saturated aqueous NaHCO3 (2×), a 1:1 mixture of the same (2×) and brine (2×). The organic phase was dried (MgSO4) and concentrated to provide an amber oil. Radial chromatography (1:1 hexane-ethyl acetate) afforded the desired compound (0.356 g, 48%) as an amber oil.

Workup

  1. extractionextracted with a 2:1 mixture of H2O and saturated aqueous NaHCO3 (2×)
  2. additiona 1:1 mixture of the same (2×) and brine (2×)
  3. dry with materialThe organic phase was dried (MgSO4)
  4. concentrationconcentrated
  5. customto provide an amber oil

Sources & evidence

ORD record
ord-ee957225ae514b9283eb8c645b3565a6
Source dataset
uspto-grants-2001_04
Patent number
US06221865B1

Reaction notes

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