Toluene → tert-Butyl 2,9-diazaspiro(5.5)undecane-9-carboxylate

HRID 2284533Notes

Reaction equation

HRID 2284533 reaction equation
C1(C)C=CC=CC=1.[H-].COCCO[Al+]OCCOC.[Na+].[H-].Cl[CH2:23][CH2:24][CH2:25][C:26]1([C:39]#[N:40])[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]1.C(=O)([O-])[O-].[Na+].[Na+]>O>[CH2:25]1[C:26]2([CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)[CH2:39][NH:40][CH2:23][CH2:24]1

Participants

6

Reactant 4

HCID 1140Toluene2×HCID 10340Sodium CarbonateHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 118021543HCID 118021543, compound2×

Product 1

HCID 46912008tert-Butyl 2,9-diazaspiro(5.5)undecane-9-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Charge 435 g of toluene then 302.1 g of sodium bis(2-methoxyethoxy)aluminum hydride to R1. Cool the mixture to −5° C.˜5° C. Charge 652.5 g of toluene and 50 g of tert-butyl 4-(3-chloropropyl)-4-cyano-piperidine-1-carboxylate into R2 and stir the mixture until clear. Add the solution of tert-butyl 4-(3-chloropropyl)-4-cyano-piperidine-1-carboxylate in R2 drop-wise to R1, control the temperature below 5° C. Stir the mixture in R1 for 0.5 hour at −5° C.˜5° C. then warm the mixture to 15˜20° C. and stir for 1˜3 hours. Charge 25 g of sodium carbonate to R2 then add 1500 g of water and cool the mixture to 0˜10° C. Add the mixture in R1 drop-wise to R2, controlling the temperature below 10° C. Warm the mixture to 20˜40° C. and stir for 10-20 mins then allow to stand for 40-60 mins Separate the aqueous layer and wash the organic layer with 2×250 g water then 297.5 g of 25% aqueous sodium chloride solution. Concentrate the organic layer to 100 g total weight below 50° C. and then add 273.0 g of acetonitrile. Concentrate the organic layer to 250 g total weight below 50° C. of title compound, tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate, which is stored as a solution: mass spectrum (m/z): 255 (M+H).

Workup

  1. temperatureCool the mixture to −5° C.˜5° C
  2. customthe temperature below 5° C
  3. stirringStir the mixture in R1 for 0.5 hour at −5° C.˜5° C.
  4. temperaturethen warm the mixture to 15˜20° C.
  5. stirringstir for 1˜3 hours
  6. temperaturecool the mixture to 0˜10° C
  7. additionAdd the mixture in R1 drop-wise to R2
  8. customthe temperature below 10° C
  9. temperatureWarm the mixture to 20˜40° C.
  10. stirringstir for 10-20 mins
  11. customSeparate the aqueous layer
  12. washwash the organic layer with 2×250 g water
  13. concentrationConcentrate the organic layer to 100 g total weight below 50° C.
  14. additionadd 273.0 g of acetonitrile
  15. concentrationConcentrate the organic layer to 250 g total weight below 50° C. of title compound, tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate, which

Sources & evidence

ORD record
ord-d524510fcd2240619e849b509a1cc46d
Source dataset
uspto-grants-2015_09
Patent number
US09145435B2

Reaction notes

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