Toluene → tert-Butyl 1-[(tert-butoxycarbonyl)amino]cyclopent-3-ene-1-carboxylate

HRID 1690819Notes

Reaction equation

HRID 1690819 reaction equation
[C:1]([OH:5])([CH3:4])([CH3:3])[CH3:2].[CH3:6][C:7]([CH3:10])([O-:9])[CH3:8].[K+].[C:12]1([CH3:18])[CH:17]=[CH:16][CH:15]=[CH:14]C=1.[N-:19]=[C:20]=[O:21].CC([O:26]C)(C)C>O>[C:1]([O:5][C:20]([NH:19][C:15]1([C:14]([O:9][C:7]([CH3:10])([CH3:8])[CH3:6])=[O:26])[CH2:16][CH:17]=[CH:12][CH2:18]1)=[O:21])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 1140TolueneHCID 6386tert-ButanolHCID 15413tert-Butyl methyl etherHCID 105034IsocyanateHCID 23665647Potassium tert-butoxide

Product 1

HCID 16218384tert-Butyl 1-[(tert-butoxycarbonyl)amino]cyclopent-3-ene-1-carboxylateYield 52%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
2.5 °C

Procedure

Add t-butanol (35 g, 471 mmol) to a solution of potassium t-butoxide (1M in THF, 471 mL, 471 mmol) under nitrogen. Cool the reaction solution was cooled to 0-5° C. and add the toluene solution containing 1-(isocyanate)-1-(tert-butoxycarbonyl)cyclopent-3-ene over 60 minutes, maintaining the temperature at 0-10° C. Warm the reaction to 23° C., stir for 2 hours, and assay by GC for the disappearance of the isocyanate starting material. Add the reaction mixture to a mixture of deionized water (1.2 L) and MTBE (1.2 L) at 15° C. Stir the solution for 20 minutes and separate the layers. Wash the organic layer with a 20% brine solution (250 mL) and separate the layers. Transfer the organic layer concentrated via distillation, to approximately 250 mL. Add heptane (500 mL) and concentrate the solution to a total volume of 250 mL. Cool the resulting slurry solution to 0° C., stir for 2 hours, and filter. Wash the filter cake with cold heptane (2×100 mL) and vacuum dry to give 34.54 g (52% yield from 1-(carboxylic acid)-1-(tert-butoxycarbonyl)cyclopent-3-ene) of 1-(tert-butoxycarbonylamino)-1-(tert-butoxycarbonyl)cyclopent-3-ene as a white solid.

Workup

  1. temperatureCool the reaction solution
  2. temperaturemaintaining the temperature at 0-10° C
  3. temperatureWarm
  4. customthe reaction to 23° C.
  5. additionAdd the reaction mixture
  6. stirringStir the solution for 20 minutes
  7. customseparate the layers
  8. washWash the organic layer with a 20% brine solution (250 mL)
  9. customseparate the layers
  10. concentrationTransfer the organic layer concentrated via distillation, to approximately 250 mL
  11. concentrationAdd heptane (500 mL) and concentrate the solution to a total volume of 250 mL
  12. temperatureCool the resulting slurry solution to 0° C.
  13. stirringstir for 2 hours
  14. filtrationfilter
  15. washWash the filter cake with cold heptane (2×100 mL) and vacuum
  16. customdry

Sources & evidence

ORD record
ord-a23995a9fda24b36925281bec918e935
Source dataset
uspto-grants-2012_04
Patent number
US08153683B2

Reaction notes

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