Iodoethane → tert-butyl (S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-yl(ethyl)carbamate

HRID 218442Notes

Reaction equation

HRID 218442 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].[H-].[Na+].[CH2:24](I)[CH3:25]>CN(C=O)C>[N:1]([CH2:4][C@@H:5]([N:14]([CH2:24][CH3:25])[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

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 58011485tert-Butyl ((2S,4R)-1-azido-7-chloro-4-(hydroxymethyl)heptan-2-yl)carbamate

Product 1

HCID 58011556tert-butyl (S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-yl(ethyl)carbamateYield 57.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 0° C. solution of crude tert-butyl (2S,4R)-1-azido-7-chloro-4-(hydroxymethyl)heptan-2-ylcarbamate (3.20 g, 10.0 mmol) in anhydrous DMF (50 mL) was added NaH (60% in mineral oil, 2.0 g, 50.0 mmol), 5 min later the temperature was allowed to warm to room temperature and stirred another 1.5 h. Ethyl iodide (4.68 g, 2.4 mL, 30.0 mmol) was added and stirred overnight at room temperature. The reaction was quenched with sat. aq. NH4Cl at 0° C., and extracted with EA (70 mL), the separated organic phase was washed with H2O (2×50 mL), brine (50 mL) successively, and dried over Na2SO4 and concentrated to afford an oil, which was purified on flash chromatography on silica gel and eluted with ethyl acetate/hexane (0-20%) to afford 1.8 g of tert-butyl (S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-yl(ethyl)carbamate. MS ESI+ve m/z: 313 (M+H)+.

Workup

  1. stirringstirred overnight at room temperature
  2. customThe reaction was quenched with sat. aq. NH4Cl at 0° C.
  3. extractionextracted with EA (70 mL)
  4. washthe separated organic phase was washed with H2O (2×50 mL), brine (50 mL) successively
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto afford an oil, which
  8. customwas purified on flash chromatography on silica gel
  9. washeluted with ethyl acetate/hexane (0-20%)

Sources & evidence

ORD record
ord-f8feaf74210a46ee857a309121ce822f
Source dataset
uspto-grants-2012_06
Patent number
US08198453B2

Reaction notes

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