Sodium Azide → (1R,2R,3R,5R,6R)-2-azido-6-fluoro-3-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester

HRID 130498Notes

Reaction equation

HRID 130498 reaction equation
[N-:1]=[N+:2]=[N-:3].[Na+].[CH2:5]([O:7][C:8]([C@@:10]1([F:26])[C@@H:12]2[CH2:13][C@@H:14]3[C@:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])([C@H:11]12)OS(=O)(=O)[O:15]3)=[O:9])[CH3:6]>CN(C)C=O.O>[CH2:22]([O:21][C:19]([C@:18]1([N:1]=[N+:2]=[N-:3])[C@H:14]([OH:15])[CH2:13][C@@H:12]2[C@H:11]1[C@@:10]2([F:26])[C:8]([O:7][CH2:5][CH3:6])=[O:9])=[O:20])[CH3:23]

Participants

5

Reactant 2

HCID 33557Sodium AzideHCID 11336666(1R,1aR,1bS,4aR,5aR)-1-fluoro-3,3-dioxotetrahydro-2,4-dioxa-3lambda6-thiacyclopropa[a]pentalene-1,1b-dicarboxylic acid diethyl ester

Product 1

HCID 11162402(1R,2R,3R,5R,6R)-2-azido-6-fluoro-3-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl esterYield 91.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

37.7 g of sodium azide was added to 109 g of (1R,1aR,1bS,4aR,5aR)-1-fluoro-3,3-dioxotetrahydro-2,4-dioxa-3λ6-thiacyclopropa[a]pentalene-1,1b-dicarboxylic acid diethyl ester dissolved in 1.10 L of N,N-dimethylformamide and 110 mL of water, and the mixture was stirred for 14 hours at 50° C. The solvent was distilled off under reduced pressure, and after the residue was dissolved in 6.48 L of diethyl ether and 177 mL of water, 516 mL of 20% (V/V) sulfuric acid was added thereto, and the mixture was stirred for 34 hours at room temperature. After the reaction solution was separated, the organic layers were twice washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate. After the desiccant was filtered off, the filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel: Wako gel C200, eluent: hexane-ethyl acetate=4:1), thereby yielding 88.5 g of (1R,2R,3R,5R,6R)-2-azido-6-fluoro-3-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester.

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. dissolutionafter the residue was dissolved in 6.48 L of diethyl ether
  3. addition177 mL of water, 516 mL of 20% (V/V) sulfuric acid was added
  4. customAfter the reaction solution was separated
  5. washthe organic layers were twice washed with a saturated aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationAfter the desiccant was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by column chromatography (silica gel: Wako gel C200, eluent: hexane-ethyl acetate=4:1)

Sources & evidence

ORD record
ord-de51faa61d314ad7acd001426e74869a
Source dataset
uspto-grants-2008_06
Patent number
US07381746B2

Reaction notes

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