Sodium hydride → [2-(N-Methyl-N-methoxycarbonyl-aminooxy)-ethyl]-carbamic acid tert-butyl ester

HRID 1987074Notes

Reaction equation

HRID 1987074 reaction equation
[CH3:1][O:2][C:3](=[O:7])[N:4]([OH:6])[CH3:5].[H-].[Na+].[C:10]([O:14][C:15]([NH:17][CH2:18][CH2:19]OS(C)(=O)=O)=[O:16])([CH3:13])([CH3:12])[CH3:11]>CN(C=O)C>[C:10]([O:14][C:15](=[O:16])[NH:17][CH2:18][CH2:19][O:6][N:4]([CH3:5])[C:3]([O:2][CH3:1])=[O:7])([CH3:13])([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 21720042Methyl hydroxy(methyl)carbamateHCID 22605302tert-Butyl N-(2-((methylsulfonyl)oxy)ethyl)carbamate

Product 1

HCID 57722702[2-(N-Methyl-N-methoxycarbonyl-aminooxy)-ethyl]-carbamic acid tert-butyl esterYield 6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of N-Hydroxy-N-methyl-carbamic acid methyl ester (5.90 g, 56.2 mmol), as prepared in the previous step, in DMF (130 mL) at 0° C. was added NaH (1.35 g, 53 mmol) in one portion. The mixture was stirred at room temperature for 15 min, then stirred on an ice bath while a solution of methanesulfonic acid 2-tert-butoxycarbonylamino-ethyl ester (10.38 g, 43 mmol) (Clagett-Dame, M., et al; Biochim. Biophys. Acta, 986:271-280, 1989) in DMF (50 mL) was added in one portion. The ice bath was removed and the mixture stirred at room temperature 23 h. The DMF was removed by rotary evaporation, the residue was diluted with half-saturated NaHCO3 (100 mL), and extracted with EtOAc (3×50 mL). The organic layers were combined, dried (Na2SO4), and concentrated. Flash chromatographic purification of the residue (3:2 hex/EtOAc) afforded 643 mg of the title compound as a colorless oil (2.59 mmol, 6% yield). 1H NMR (300 Hz, CDCl3) δ 5.38 (br s, 1H), 3.89 (t, J=5.1 Hz, 2H), 3.78 (s, 3H), 3.34 (q, J=5.5 Hz, 2H), 3.14 (s, 3H), 1.45 (s, 9H); LC/MS (m/z) [MH+−Boc] 149 (calculated for C5H13N2O3, 149.1).

Workup

  1. additionwas added in one portion
  2. customThe ice bath was removed
  3. stirringthe mixture stirred at room temperature 23 h
  4. customThe DMF was removed by rotary evaporation
  5. additionthe residue was diluted with half-saturated NaHCO3 (100 mL)
  6. extractionextracted with EtOAc (3×50 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customFlash chromatographic purification of the residue (3:2 hex/EtOAc)

Sources & evidence

ORD record
ord-350769db5cef4f24be2e68324101c9bf
Source dataset
uspto-grants-2009_06
Patent number
US07550474B2

Reaction notes

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