Acetone → HCID 58168719, compound

HRID 38776Notes

Reaction equation

HRID 38776 reaction equation
[F:1][C:2]12[CH2:12][C:6]3([OH:13])[CH2:7][C:8]([F:11])([CH2:10][C:4](C(O)=O)([CH2:5]3)[CH2:3]1)[CH2:9]2.[CH3:17][C:18]([CH3:20])=O.Cl[C:22]([O:24][CH2:25][CH3:26])=[O:23].[N-:27]=[N+]=[N-].[Na+].[CH2:31](N(CC)CC)[CH3:32]>O>[F:11][C:8]12[CH2:7][C:6]3([OH:13])[CH2:12][C:2]([F:1])([CH2:3][C:4]([NH:27][C:22](=[O:23])[O:24][CH2:25][C:26]4[CH:32]=[CH:31][CH:20]=[CH:18][CH:17]=4)([CH2:5]3)[CH2:10]1)[CH2:9]2

Participants

7

Reactant 5

HCID 180AcetoneHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 33557Sodium AzideHCID 54288587HCID 54288587, compound

Product 1

HCID 58168719HCID 58168719, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a mixture of 3,5-difluoro-7-hydroxy adamantane-1-carboxylic acid (1.04 g) and acetone (10 mL) were added triethylamine (1.25 mL) and ethyl chloroformate (860 μL) under ice-cooling, followed by stirring at the same temperature for 30 minutes. To the reaction mixture was added a solution of sodium azide (437 mg) in water (5 mL) under ice-cooling, followed by stirring at the same temperature for 80 minutes. To the reaction mixture was added water and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with 1 M hydrochloric acid, water, and saturated brine in this order, and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. To the residue were added toluene (12 mL) and 1,4-dioxane (6 mL), followed by stirring at 85° C. for 15 minutes, and then benzyl alcohol (581 mg) and triethylamine (750 μL) were added thereto, followed by stirring at 95° C. for 4 hours. The mixture was cooled to room temperature, and then water was added thereto, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with 1 M hydrochloric acid, water, and saturated brine in this order, and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate) to obtain benzyl (3,5-difluoro-7-hydroxyadamantan-1-yl)carbamate (1.15 g) as a white powder.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringby stirring at the same temperature for 80 minutes
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washThe organic layer was washed with 1 M hydrochloric acid, water, and saturated brine in this order
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. additionTo the residue were added toluene (12 mL) and 1,4-dioxane (6 mL)
  9. stirringby stirring at 85° C. for 15 minutes
  10. additionbenzyl alcohol (581 mg) and triethylamine (750 μL) were added
  11. stirringby stirring at 95° C. for 4 hours
  12. additionwater was added
  13. extractionthe aqueous layer was extracted with ethyl acetate
  14. washThe organic layer was washed with 1 M hydrochloric acid, water, and saturated brine in this order
  15. dry with materialdried over anhydrous magnesium sulfate
  16. customthe solvent was evaporated under reduced pressure
  17. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)

Sources & evidence

ORD record
ord-7035e5575b0d44c98d2ebd3ccef69d78
Source dataset
uspto-grants-2013_09
Patent number
US08524727B2

Reaction notes

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