Dimethylformamide → Benzyl 3-[(tert-butoxycarbonyl)(n-propyl)amino]azetidine-1-carboxylate

HRID 43905Notes

Reaction equation

HRID 43905 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:12][N:11]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:25](I)[CH2:26][CH3:27].CN(C=O)C>C1COCC1.O>[C:1]([O:5][C:6]([N:8]([CH2:25][CH2:26][CH3:27])[CH:9]1[CH2:10][N:11]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:12]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 336431-IodopropaneHCID 67548302HCID 67548302, compound

Product 1

HCID 67548639Benzyl 3-[(tert-butoxycarbonyl)(n-propyl)amino]azetidine-1-carboxylateYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of benzyl 3-[(tert-butoxycarbonyl)amino]azetidine-1-carboxylate obtained in Example (227a) (472 mg, 1.54 mmol) in THF (5 mL) was added to a suspension of sodium hydride (55%) (134 mg, 3.08 mmol) in THF (10 mL) at 0° C. Subsequently, propyl iodide (0.75 mL, 7.70 mmol) was added at 0° C., and the mixture was stirred at room temperature for 70 minutes. THF (4 mL) and DMF (5 mL) were added, followed by further stirring for 18 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. Thereafter, the combined organic layers were washed with brine and dried over anhydrous magnesium sulfate. Following filtration, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=2/1) to obtain 499 mg of the title compound as a colorless oily substance (93%).

Workup

  1. stirringby further stirring for 18 hours
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThereafter, the combined organic layers were washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-72a104d2301d4e94b025ff44f88049d0
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

Loading…