Sodium Azide → 749934-78-9

HRID 858875Notes

Reaction equation

HRID 858875 reaction equation
Cl[CH2:2][CH2:3][C:4]([CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5].[N-:11]=[N+]=[N-].[Na+].[C:15]([O:22]C(OC(C)(C)C)=O)(=O)[O:16][C:17]([CH3:20])([CH3:19])[CH3:18]>CN(C=O)C.C(OCC)(=O)C.O>[C:17]([O:16][C:15](=[O:22])[NH:11][CH2:2][CH2:3][C:4]([CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5])([CH3:20])([CH3:19])[CH3:18]

Participants

7

Reactant 3

HCID 33557Sodium AzideHCID 90495Di-tert-butyl dicarbonateHCID 55298626HCID 55298626, compound

Product 1

HCID 58762663749934-78-9Yield 38.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3-chloro-1-cyclopentyl-propan-1-one (2.913 g, 18.1 mmol) from Step 1 above in DMF (40 mL) was added sodium azide (1.77 g, 27.2 mmol). The reaction was heated to 70° C. for 3 hours. The reaction was cooled to room temperature, and then diluted with 100 mL of ethyl acetate and 100 mL of water. The layers were separated, and the aqueous was extracted with 2×50 mL of ethyl acetate. The organic layer was then washed with 2×50 mL of water. The organic layer was dried over sodium sulfate, filtered, and concentrated to an oil. The oil was then dissolved in ethanol (75 mL) and TFA was added (3 mL). To this solution was added 10% Pd/C (300 mg). The slurry was stirred under a hydrogen atmosphere for 2 hours. The solids were removed by filtration, and the organic was concentrated by rotary evaporation to a black oil. The black oil was dissolved in THF (100 mL) and TEA (7.5 mL) and di-tert-butyl pyrocarbonate (1 M in THF, 40 mL, 40 mmol) were added. The reaction was stirred at room temperature for 18 hours, and then concentrated by rotary evaporation. The crude oil was purified by flash chromatography to yield the product (1.677 g, 38%).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous was extracted with 2×50 mL of ethyl acetate
  4. washThe organic layer was then washed with 2×50 mL of water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to an oil
  8. dissolutionThe oil was then dissolved in ethanol (75 mL)
  9. additionTFA was added (3 mL)
  10. additionTo this solution was added 10% Pd/C (300 mg)
  11. customThe solids were removed by filtration
  12. concentrationthe organic was concentrated by rotary evaporation to a black oil
  13. dissolutionThe black oil was dissolved in THF (100 mL)
  14. stirringThe reaction was stirred at room temperature for 18 hours
  15. concentrationconcentrated by rotary evaporation
  16. customThe crude oil was purified by flash chromatography

Sources & evidence

ORD record
ord-cda9b20163d34a59a19e7245ccd22268
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Reaction notes

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