4-Methylmorpholine → HCID 18665834, compound

HRID 399343Notes

Reaction equation

HRID 399343 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]([CH2:38][C:39]2[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=2)[C@H:13]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][CH2:27][C:28]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=[CH:30][CH:29]=3)=[O:24])[CH2:19][CH2:18]2)[C:14](O)=[O:15])(=[O:11])=[O:10])=[CH:5][CH:4]=1.[C:45]([O:49][NH2:50])([CH3:48])([CH3:47])[CH3:46].CN1CCOCC1.ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl.C(OCC)(=O)C>[C:45]([O:49][NH:50][C:14](=[O:15])[C@H:13]([N:12]([S:9]([C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=1)(=[O:11])=[O:10])[CH2:38][C:39]1[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=1)[CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][CH2:27][C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH:31]=[CH:30][CH:29]=2)=[O:24])[CH2:19][CH2:18]1)([CH3:48])([CH3:47])[CH3:46]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2777907O-tert-butylhydroxylamineHCID 18665818HCID 18665818, compound

Product 1

HCID 18665834HCID 18665834, compoundYield 72.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the crude 2-(R)-[(4-methoxybenzenesulfonyl)(4-picolyl)amino]-2-[(N-(2-(1-naphthyl)-ethoxycarbonyl))-4-piperidinyl] acetic acid (6.02 mmol) in methylene chloride (150 ml) is added O-t-butylhydroxylamine (2.27 g, 18.06 mmol), N-methylmorpholine (3.65 g, 36.12 mmol), 1-hydroxy-7-azabenzotriazole (819 mg, 6.02 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.5 g, 7.83 mmol). The reaction mixture is stirred at room temperature for 1.5 hours, diluted with ethyl acetate and washed with water. The aqueous layer is extracted with ethyl acetate, the combined organic layers are washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude product is purified by silica gel chromatography (2% methanol in methylene chloride) to provide N-(t-butyloxy)-2-(R)-[(4-methoxybenzenesulfonyl) (4-picolyl)amino]-2-[(N-(2-(1-naphthyl)-ethoxycarbonyl))-4-piperidinyl]acetamide (3 g).

Workup

  1. washwashed with water
  2. extractionThe aqueous layer is extracted with ethyl acetate
  3. washthe combined organic layers are washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by silica gel chromatography (2% methanol in methylene chloride)

Sources & evidence

ORD record
ord-16c9e375646a42a0859cf8f68faafcfc
Source dataset
uspto-grants-1998_10
Patent number
US05817822

Reaction notes

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