Hydrochloric Acid → (1S*,5S*)-3-(4-bromo-2-ethylphenyl)-1-ethoxymethyl-8-oxabicyclo[3.2.1]octane-2,4-dione

HRID 341659Notes

Reaction equation

HRID 341659 reaction equation
[CH2:1]([O:3][CH2:4][C@@:5]12[O:12][C@@H:9]([CH2:10][CH2:11]1)[C:8](=[O:13])[CH2:7][C:6]2=[O:14])[CH3:2].C(Cl)(Cl)Cl.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Br:31][C:32]1[CH:37]=[CH:36][C:35]([Pb+3])=[C:34]([CH2:39][CH3:40])[CH:33]=1.Cl>CN(C)C1C=CN=CC=1.C1(C)C=CC=CC=1>[Br:31][C:32]1[CH:37]=[CH:36][C:35]([CH:7]2[C:8](=[O:13])[C@H:9]3[O:12][C@:5]([CH2:4][O:3][CH2:1][CH3:2])([CH2:11][CH2:10]3)[C:6]2=[O:14])=[C:34]([CH2:39][CH3:40])[CH:33]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6212ChloroformHCID 68730659(1S*,5S*)-1-ethoxymethyl-8-oxabicyclo[3.2.1]octane-2,4-dioneHCID 178476529HCID 178476529, compound

Product 1

HCID 68732175(1S*,5S*)-3-(4-bromo-2-ethylphenyl)-1-ethoxymethyl-8-oxabicyclo[3.2.1]octane-2,4-dioneYield 29.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

(1S*,5S*)-1-Ethoxymethyl-8-oxabicyclo[3.2.1]octane-2,4-dione (0.8 g, 4.04 mmol) and 4-dimethylaminopyridine (2.4 g, 19.67 mmol) are added to a mixture of chloroform (16 ml) and toluene (4 ml). The reaction mixture is flushed with nitrogen for 15 minutes at ambient temperature. 4-Bromo-2-ethylphenyllead triacetate (2.49 g, 4.38 mmol) is added in one portion and the reaction mixture is stirred and heated to 80° C. (pre-heated oil bath) under an atmosphere of nitrogen for 1 hour. The reaction mixture is cooled to room temperature, acidified to pH 1 with 2N aqueous hydrochloric acid, filtered through a plug of diatomaceous earth and the two phases are separated. The aqueous phase is extracted with dichloromethane (2×25 ml), the organic phases are combined, washed with water, and dried over anhydrous sodium sulfate. The mixture is filtered, and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give (1S*,5S*)-3-(4-bromo-2-ethylphenyl)-1-ethoxymethyl-8-oxabicyclo[3.2.1]octane-2,4-dione as white solid (0.45 g).

Workup

  1. customThe reaction mixture is flushed with nitrogen for 15 minutes at ambient temperature
  2. temperature(pre-heated oil bath) under an atmosphere of nitrogen for 1 hour
  3. temperatureThe reaction mixture is cooled to room temperature
  4. filtrationfiltered through a plug of diatomaceous earth
  5. customthe two phases are separated
  6. extractionThe aqueous phase is extracted with dichloromethane (2×25 ml)
  7. washwashed with water
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationThe mixture is filtered
  10. customthe filtrate is evaporated under reduced pressure
  11. customThe residue is purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-be1528acdd5340d9847723098b6e700f
Source dataset
uspto-grants-2014_11
Patent number
US08895761B2

Reaction notes

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