Dimethyl Sulfate → tert-Butyl ((S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-yl)(methyl)carbamate

HRID 218439Notes

Reaction equation

HRID 218439 reaction equation
[N:1]([CH2:4][C@@H:5]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:6][C@H:7]([CH2:12][OH:13])[CH2:8][CH2:9][CH2:10]Cl)=[N+:2]=[N-:3].[CH3:22]OS(OC)(=O)=O>CN(C=O)C>[N:1]([CH2:4][C@@H:5]([N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:6][C@H:7]1[CH2:8][CH2:9][CH2:10][O:13][CH2:12]1)=[N+:2]=[N-:3]

Participants

4

Reactant 2

HCID 6497Dimethyl SulfateHCID 58011485tert-Butyl ((2S,4R)-1-azido-7-chloro-4-(hydroxymethyl)heptan-2-yl)carbamate

Product 1

HCID 58011481tert-Butyl ((S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-yl)(methyl)carbamateYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

The tert-butyl (2S,4R)-1-azido-7-chloro-4-(hydroxymethyl)heptan-2-ylcarbamate (1.59 g, 4.97 mmol, 1.0 equiv) was dissolved in 15 mL of DMF and the solution cooled to 0° C. A solution of NaNTMS2 (1.0 M, 14.9 mmol, 3.0 equiv) was added via syringe at such a rate that the internal reaction temperature remains below 5° C. After stirring for 2 h LC/MS analysis showed formation of the cyclised product. Dimethylsulfate (940 mg, 0.71 mL, 7.5 mmol, 1.5 equiv) was added and the reaction mixture stirred overnight with concomitant warming to ambient temperature. LC/MS analysis showed formation of the desired methylated carbamate. The reaction was quenched by addition of 10% K2CO3 solution (˜30 mL) and the mixture stirred for 0.5 h. The volatile materials were removed in vacuo and the residue partitioned between EtOAc/water. The layers were separated and the organic layer washed with brine, dried over Na2SO4, filtered and evaporated. The product was purified by flash chromatography on silica (40 g), eluting with 0-7% EtOAc in hexanes. This afforded 1.21 g (82% yield) of the desired tert-butyl (S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-yl(methyl)carbamate as a colorless liquid.

Workup

  1. additionA solution of NaNTMS2 (1.0 M, 14.9 mmol, 3.0 equiv) was added via syringe at such a rate that the internal reaction temperature
  2. customremains below 5° C
  3. stirringthe reaction mixture stirred overnight
  4. temperaturewith concomitant warming to ambient temperature
  5. customThe reaction was quenched by addition of 10% K2CO3 solution (˜30 mL)
  6. stirringthe mixture stirred for 0.5 h
  7. customThe volatile materials were removed in vacuo
  8. customthe residue partitioned between EtOAc/water
  9. customThe layers were separated
  10. washthe organic layer washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. customevaporated
  14. customThe product was purified by flash chromatography on silica (40 g)
  15. washeluting with 0-7% EtOAc in hexanes

Sources & evidence

ORD record
ord-4b207801adc5432595ccdc5059020fd1
Source dataset
uspto-grants-2012_06
Patent number
US08198453B2

Reaction notes

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