Acetonitrile → HCID 14925135, compound

HRID 1850148Notes

Reaction equation

HRID 1850148 reaction equation
CON(C)[C:4](=[O:17])[C@@H:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:6]([CH3:8])[CH3:7].C[Li].[CH3:21]C#N>C1COCC1.C(=O)=O.CCOC(C)=O.O>[CH3:8][CH:6]([C@H:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:14])[CH3:15])[C:4](=[O:17])[CH3:21])[CH3:7]

Participants

8

Reactant 3

HCID 6342AcetonitrileHCID 10083961Boc-L-leucine N,O-dimethylhydroxamideHCID 178418348HCID 178418348, compound

Product 1

HCID 14925135HCID 14925135, compound

Reagents, catalysts & solvents 4

HCID 280Carbon DioxideSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-tert-butyl 1-(methoxy(methyl)amino)-3-methyl-1-oxobutan-2-ylcarbamate (4.23 g, 16.25 mmol) in THF (100 mL) at −70° C. was added drop wise methyl lithium (1.071 g, 48.7 mmol). Cold bath was replaced with −40° C. bath (MeCN in dry ice) removed and the reaction was stirred for 4 hours. Saturated NH4Cl solution (10 mL) was then added cautiously to quench the reaction. The reaction mixture was then allowed to warm to room temperature, and diluted with EtOAc (100 mL) and water (50 mL). The phases were separated and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organics were then dried (Na2SO4) and concentrated under reduced pressure. The residue was purified via silica gel flash chromatography (10-50% EtOAc-Hexanes) to afford the desired product as a white solid (3.01 g). LCMS m/z 238.2 (M+Na)+, Rt 0.78 min.

Workup

  1. customwas replaced with −40° C.
  2. customremoved
  3. additionSaturated NH4Cl solution (10 mL) was then added cautiously
  4. customto quench
  5. customthe reaction
  6. customThe phases were separated
  7. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  8. dry with materialThe combined organics were then dried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified via silica gel flash chromatography (10-50% EtOAc-Hexanes)

Sources & evidence

ORD record
ord-35b54357728444a0be6d3d1905c83749
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

Loading…