Triethylamine → tert-butyl 4-[(E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-enyl]-4,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 2284536Notes

Reaction equation

HRID 2284536 reaction equation
Cl.C1C2(CCN(C(OC(C)(C)C)=O)CC2)CNCC1.C(=O)([O-])[O-].[Cs+].[Cs+].BrCCC#C.[CH2:31]([N:35]1[CH2:40][C:39]2([CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42][CH2:41]2)[CH2:38][CH2:37][CH2:36]1)[CH2:32][C:33]#[CH:34].C(N(CC)CC)C.[CH3:60][C:61]1([CH3:68])[C:65]([CH3:67])([CH3:66])[O:64][BH:63][O:62]1>C(OCC)(=O)C.ClCCl.[Cl-].[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Zr+2].C(#N)C>[CH3:60][C:61]1([CH3:68])[C:65]([CH3:67])([CH3:66])[O:64][B:63](/[CH:34]=[CH:33]/[CH2:32][CH2:31][N:35]2[CH2:40][C:39]3([CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42][CH2:41]3)[CH2:38][CH2:37][CH2:36]2)[O:62]1

Participants

11

Reactant 6

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 110734644-Bromobut-1-yneHCID 71464197Tert-butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate hydrochlorideHCID 86701859tert-Butyl 2-(but-3-yn-1-yl)-2,9-diazaspiro[5.5]undecane-9-carboxylate

Product 1

HCID 86701860tert-butyl 4-[(E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-enyl]-4,9-diazaspiro[5.5]undecane-9-carboxylateYield 67.3%

Reagents, catalysts & solvents 4

HCID 131724019Zirconocene chlorideCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (46.07 mmol) and cesium carbonate (115.2 mmol) to a solution of acetonitrile (200 mL). After stirring at room temperature for 20 minutes, add 4-bromobutyne (69.1 mmol) and heat the mixture to reflux with stirring overnight. Cool to room temperature and dilute with ethyl acetate (200 mL). Filter the reaction through a glass frit rinsing with ethyl acetate (2×100 mL). Concentrate the crude mixture under reduced pressure, then add ethyl acetate (200 mL) and wash the organics with water (200 mL) and brine (200 mL). Dry the organics over sodium sulfate, filter, and concentrate under reduced pressure to yield crude tert-butyl 4-but-3-ynyl-4,9-diazaspiro[5.5]undecane-9-carboxylate (13.6 g, 44.4 mmol): MS (m/z): 307.2 (M+H). To a round bottom flask under nitrogen, add tert-butyl 4-but-3-ynyl-4,9-diazaspiro[5.5]undecane-9-carboxylate (44.4 mmol), triethylamine (4.44 mmol), zirconocene chloride (4.44 mmol), and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (48.8 mmol). Heat this mixture to 60° C. for 3 hours, then stir overnight at room temperature. Dissolve the mixture in dichloromethane (20 mL) and purify by flash chromatography (330 g silica gel cartridge) eluting with 15-85% ethyl acetate in hexanes to yield the final title compound, tert-butyl 4-[(E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-enyl]-4,9-diazaspiro[5.5]undecane-9-carboxylate (29.9 mmol) as a light yellow oil: MS (m/z): 435.2 (M+H).

Workup

  1. temperatureheat the mixture
  2. temperatureto reflux
  3. stirringwith stirring overnight
  4. temperatureCool to room temperature
  5. filtrationFilter
  6. customthe reaction through a glass frit
  7. washrinsing with ethyl acetate (2×100 mL)
  8. concentrationConcentrate the crude mixture under reduced pressure
  9. washadd ethyl acetate (200 mL) and wash the organics with water (200 mL) and brine (200 mL)
  10. dry with materialDry the organics over sodium sulfate
  11. filtrationfilter
  12. concentrationconcentrate under reduced pressure
  13. customto yield crude tert-butyl 4-but-3-ynyl-4,9-diazaspiro[5.5]undecane-9-carboxylate (13.6 g, 44.4 mmol)
  14. temperatureHeat this mixture to 60° C. for 3 hours
  15. stirringstir overnight at room temperature
  16. custompurify by flash chromatography (330 g silica gel cartridge)
  17. washeluting with 15-85% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-2c3f103c5a6e4287b01810d2aa8a6d80
Source dataset
uspto-grants-2015_09
Patent number
US09145435B2

Reaction notes

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