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

HRID 2366516Notes

Reaction equation

HRID 2366516 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[CH2:8]1[C:13]2([CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH2:12][NH:11][CH2:10][CH2:9]1.Br[CH2:27][CH2:28][C:29]#[CH:30]>C(#N)C>[CH2:30]([N:11]1[CH2:12][C:13]2([CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH2:18]2)[CH2:8][CH2:9][CH2:10]1)[CH2:29][C:28]#[CH:27]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 110734644-Bromobut-1-yneHCID 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 98%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Cesium carbonate (46.66 g, 143.21 mmol) is added to a suspension of tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (16.66 g, 57.28 mmoles) in acetonitrile (167 mL). The mixture is stirred for 10 minutes at ambient temperature then 4-bromobutyne (6.45 mL, 68.74 mmol) is added. The reaction is heated to reflux and stirred for 18 hours. The mixture is cooled and concentrated under reduced pressure. The residue is partitioned between water (200 mL) and ethyl acetate (150 mL). The phases are separated and the aqueous layer is extracted with ethyl acetate (100 mL). The combined organic layers are washed with water (200 mL), then brine (150 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to give the title compound (17.2 g, 98% yield). 1H NMR (300.11 MHz, CDCl3): δ 3.43-3.31 (m, 4H), 2.53-2.48 (m, 2H), 2.37-2.29 (m, 4H), 2.20 (s, 2H), 1.94 (t, J=2.6 Hz, 1H), 1.44 (s, 17H).

Workup

  1. temperatureThe reaction is heated
  2. temperatureto reflux
  3. stirringstirred for 18 hours
  4. temperatureThe mixture is cooled
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is partitioned between water (200 mL) and ethyl acetate (150 mL)
  7. customThe phases are separated
  8. extractionthe aqueous layer is extracted with ethyl acetate (100 mL)
  9. washThe combined organic layers are washed with water (200 mL)
  10. dry with materialbrine (150 mL), dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1a43b68cb04f4d13a829944c1ab65160
Source dataset
uspto-grants-2014_04
Patent number
US08697849B2

Reaction notes

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