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

HRID 1625938Notes

Reaction equation

HRID 1625938 reaction equation
Cl.[CH2:2]1[C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6][NH:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:27][CH2:28][C:29]#[CH:30]>C(#N)C>[CH2:30]([N:5]1[CH2:6][C:7]2([CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH2:12]2)[CH2:2][CH2:3][CH2:4]1)[CH2:29][C:28]#[CH:27]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 110734644-Bromobut-1-yne2×HCID 71464197Tert-butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride

Product 1

HCID 86701859tert-Butyl 2-(but-3-yn-1-yl)-2,9-diazaspiro[5.5]undecane-9-carboxylateYield 72%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (170.00 g, 584.53 mmoles), cesium carbonate (476.13 g, 1.46 moles), and 4-bromobutyne (93.28 g, 701.43 mmoles) in acetonitrile (1.70 L) is heated to 60° C. and stirred at this temperature overnight. Further 4-bromobutyne (46.64 g, 350.72 mmoles) is added and the mixture is stirred at 60° C. overnight. The mixture is cooled and filtered. The filtrate is concentrated under reduced pressure and the residue dissolved in ethyl acetate (500 mL), washed with water (1 L), and saturated aqueous sodium chloride (1 L), then dried over MgSO4, and filtered. The filtrate is concentrated under reduced pressure and the residue is purified by silica column chromatography eluting with 20 to 70% ethyl acetate in dichloromethane to provide the title compound (129 g, 72% yield). Mass spectrum (m/z): 307.25 (M+1).

Workup

  1. stirringthe mixture is stirred at 60° C. overnight
  2. temperatureThe mixture is cooled
  3. filtrationfiltered
  4. concentrationThe filtrate is concentrated under reduced pressure
  5. dissolutionthe residue dissolved in ethyl acetate (500 mL)
  6. washwashed with water (1 L), and saturated aqueous sodium chloride (1 L)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated under reduced pressure
  10. customthe residue is purified by silica column chromatography
  11. washeluting with 20 to 70% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-2bad867ee657407b94547cbb3190a8a3
Source dataset
uspto-grants-2014_07
Patent number
US08785404B2

Reaction notes

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