1,2-Dichloroethane → Tert-butyl (R)-(1-(3-methyl-1,2,4-oxadiazol-5-YL)ethyl)carbamate

HRID 1257521Notes

Reaction equation

HRID 1257521 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:11]([OH:13])=O)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:14](=[N:17]O)([NH2:16])[CH3:15].C(Cl)CCl.C(OCC)(=O)C>O1CCOCC1.CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([C:11]1[O:13][N:17]=[C:14]([CH3:15])[N:16]=1)[CH3:10])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 8857Ethyl AcetateHCID 30926N-HydroxyacetamidineHCID 637606BOC-D-alanine

Product 1

HCID 86657025Tert-butyl (R)-(1-(3-methyl-1,2,4-oxadiazol-5-YL)ethyl)carbamateYield 24.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of N-(tert-butoxycarbonyl)-D-alanine (20 g, 106 mmol), acetamide oxime (17.3 g, 234 mmol) in 120 mL of 1,4-dioxane and 30 mL of N,N-dimethylformamide were added EDC (44.8 g, 234 mmol). The mixture was heated at 60° C. for 4 h and at 100° C. for 16 h. After cooling to ambient temperature, 300 mL of ethyl acetate was added into the reaction. The organic layer was washed by saturated sodium bicarbonate (2×). The organic were dried over magnesium sulfate, filtered and concentrated. The residue was purified by 0-10% methanol/dichloromethane gradient on silica column to give pure tert-butyl[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]carbamate (6.0 g). MS172.1 ((M-t-Butyl+H)+1).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. washThe organic layer was washed by saturated sodium bicarbonate (2×)
  3. dry with materialThe organic were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by 0-10% methanol/dichloromethane gradient on silica column

Sources & evidence

ORD record
ord-d2489cef039b46069362e40bb60eb952
Source dataset
uspto-grants-2013_06
Patent number
US08461185B2

Reaction notes

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