Potassium Carbonate → tert-Butyl 2-(but-3-yn-1-yl)-2,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 2284534Notes

Reaction equation

HRID 2284534 reaction equation
[CH2:1]1[C:6]2([CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)[CH2:5][NH:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:26][CH2:27][C:28]#[CH:29].C(O)(=O)C(O)=O.CC(C)=O>CC#N>[CH2:29]([N:4]1[CH2:5][C:6]2([CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:10][CH2:11]2)[CH2:1][CH2:2][CH2:3]1)[CH2:28][C:27]#[CH:26]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 110734644-Bromobut-1-yneHCID 46912008tert-Butyl 2,9-diazaspiro(5.5)undecane-9-carboxylateHCID 88629647Oxalic acid acetone

Product 1

HCID 86701859tert-Butyl 2-(but-3-yn-1-yl)-2,9-diazaspiro[5.5]undecane-9-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
67.5 °C

Procedure

Charge in order, 23.7 g of CH3CN, 10 g of tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate, 9.2 g of K2CO3 then 8.4 g of 4-bromobut-1-yne to R1. Heat the mixture to 65-70° C. and stir the mixture at 65-70° C. for 12-18 hours. Concentrate the mixture to a total weight of 30-40 g below 50° C., then add 76 g of MTBE and 50 g of water. Stir the mixture at 20-25° C. for 30 mins then allow to stand to 30 mins Separate the aqueous. Preopare a solution of 1 g of KOH in 49 g of water and add this to the organic layer at 20-25° C. Stir the mixture at 20-25° C. for 30 mins then allow to stand for 20-30 mins at 20-25° C. Separate the aqueous layer out and wash the organics with 50 g of water. Concentrate the organic phase to 40-50 g total weight below 50° C. in R1. Prepare a solution of 7.4 g of oxalic acid dihydrate in 39.5 g of acetone, then add drop wise the oxalic acid/acetone solution into R1 at 20-25° C. Stir the suspension at 20-25° C. for 2-3 hours then filter. Wash the cake with 15.2 g of MTBE. Slurry the cake in 89 g of THF and stir the mixture at 50° C. for 6-8 hours. Cool the mixture to 20-25° C. and filter. Wash the cake with 17.8 g of THF. Again, slurry the cake in 89 g of THF and stir the mixture at 50° C. for 6-8 hours. Cool the mixture to 20-25° C. and filter. Wash the cake with 17.8 g of THF. Dry the cake under vacuum at 50-60° C. for 16-18 hours to provide the title compound, tert-butyl 4-but-3-ynyl-4,9-diazaspiro[5.5]undecane-9-carboxylate; oxalic acid.

Workup

  1. concentrationConcentrate the mixture to a total weight of 30-40 g below 50° C.
  2. additionadd 76 g of MTBE and 50 g of water
  3. stirringStir the mixture at 20-25° C. for 30 mins
  4. waitto stand to 30 mins
  5. customSeparate the aqueous
  6. additionPreopare a solution of 1 g of KOH in 49 g of water and add this to the organic layer at 20-25° C
  7. stirringStir the mixture at 20-25° C. for 30 mins
  8. waitto stand for 20-30 mins at 20-25° C
  9. customSeparate the aqueous layer out and
  10. washwash the organics with 50 g of water
  11. concentrationConcentrate the organic phase to 40-50 g total weight below 50° C. in R1
  12. customPrepare a solution of 7.4 g of oxalic acid dihydrate in 39.5 g of acetone
  13. stirringStir the suspension at 20-25° C. for 2-3 hours
  14. filtrationthen filter
  15. washWash the cake with 15.2 g of MTBE
  16. stirringstir the mixture at 50° C. for 6-8 hours
  17. temperatureCool the mixture to 20-25° C.
  18. filtrationfilter
  19. washWash the cake with 17.8 g of THF
  20. stirringstir the mixture at 50° C. for 6-8 hours
  21. temperatureCool the mixture to 20-25° C.
  22. filtrationfilter
  23. washWash the cake with 17.8 g of THF
  24. customDry the cake under vacuum at 50-60° C. for 16-18 hours

Sources & evidence

ORD record
ord-cb483c7b47954e9b9acd69934da13995
Source dataset
uspto-grants-2015_09
Patent number
US09145435B2

Reaction notes

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