4-Methylmorpholine → HCID 86750057, compound

HRID 1080848Notes

Reaction equation

HRID 1080848 reaction equation
CN.[C:3]([N:10]1[CH2:17][CH2:16][CH2:15][C@H:11]1[C:12](O)=O)([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[C:18]([NH:28][CH2:29][CH2:30][CH2:31][C:32]([OH:34])=O)([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19].C1C=CC2N(O)N=[N:41]C=2C=1.CCN=C=NCCCN(C)C.CN1CCOCC1>CN(C)C=O>[O:34]=[C:32]([NH:41][CH2:12][C@@H:11]1[CH2:15][CH2:16][CH2:17][N:10]1[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])[CH2:31][CH2:30][CH2:29][NH:28][C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 211844-(((Benzyloxy)carbonyl)amino)butanoic acidHCID 757711-HydroxybenzotriazoleHCID 22867970HCID 22867970, compound

Product 1

HCID 86750057HCID 86750057, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Part B N-BOC-L-proline methylamine (1.04 g, 5.2 mmol) and N-CBZ-4-aminobutyric acid (1.24 g, 5.2 mmol) were dissolved in dimethyl formamide (DMF) (20 mL) at room temperature (RT). HOBT (702 mg, 5.2 mmol), WSC (995 mg, 5.2 mmol) and NMM (570 μL, 5.2 mmol) were added. The reaction was stirred for 16 hours (h), partitioned between ethyl acetate(50 mL) and 10% KHSO4 (100 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL), and the organic layers were combined. The combined organic layers were washed with saturated NaHCO3 (50 mL) and saturated NaCl (50 mL), dried over magnesium sulfate and concentrated in vacuo to provide an oil. The crude material was purified by chromatography on silica gel. Elution with ethyl acetate:hexanes(2:1) followed by ethyl acetate gave title compound, (1.809 g, 83%) as a viscous oil which was characterized by NMR and used in the next step.

Workup

  1. custompartitioned between ethyl acetate(50 mL) and 10% KHSO4 (100 mL)
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  3. washThe combined organic layers were washed with saturated NaHCO3 (50 mL) and saturated NaCl (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto provide an oil
  7. customThe crude material was purified by chromatography on silica gel
  8. washElution with ethyl acetate:hexanes(2:1)

Sources & evidence

ORD record
ord-d4adcf1e2c2f474cbfade890780e2cba
Source dataset
uspto-grants-1996_12
Patent number
US05583146

Reaction notes

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