Reaktion #12014

ord-90af6704e9c3417f9f4a191d574bb4d4

Reaktionsgleichung

B1C2CCCC1CCC2
9-borabicyclo[3.3.1]nonane
C#CCBr
propargyl bromide
C[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]2Cc3ccc(Br)nc3N21
(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester
C[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]2Cc3ccc(Br)nc3N21
intermediate b
C[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]2Cc3ccc(Br)nc3N21
(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester
[Na+].[OH-]
sodium hydroxide
C[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]2Cc3ccc(C4CC4)nc3N21
desired product
Ausbeute 35.2%
C[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]2Cc3ccc(C4CC4)nc3N21
(4R,9aR)-6-Cyclopropyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester
Ausbeute 35.2%

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Temperaturwas heated
  2. 2
    Temperaturto reflux for 2 h
  3. 3
    workup.ADDITIONwas added
  4. 4
    TemperaturThe mixture was heated
  5. 5
    Temperaturto reflux for 16 h
  6. 6
    Temperaturthen cooled to room temperature
  7. 7
    Sonstigethe phases were separated
  8. 8
    ExtraktionThe aqueous phase was extracted three times with ethyl acetate
  9. 9
    Waschenthe combined organic layers were washed with 1M aqueous sodium hydroxide solution and brine
  10. 10
    Trocknendried over magnesium sulfate
  11. 11
    Filtrationfiltered
  12. 12
    Sonstigeevaporated
  13. 13
    SonstigeThe residue was purified by chromatography on silica gel (0.032–0.063 mm) with n-hexane as eluant

Vorschrift

A suspension of 150.0 mg (1.23 mmol) 9-borabicyclo[3.3.1]nonane and 47 μl (0.62 mmol) propargyl bromide in 1 ml tetrahydrofuran was heated to reflux for 2 h. The mixture was cooled to room temperature then 0.61 ml (1.83 mmol) of a degassed 3M sodium hydroxide solution was added and after 1 h a mixture of 0.20 g (0.54 mmol) (4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (Example 5, intermediate b) and 19.0 mg tetrakis(triphenylphosphine)palladium in 1 ml tetrahydrofuran was added. The mixture was heated to reflux for 16 h then cooled to room temperature and poured into water and ethyl acetate; the phases were separated. The aqueous phase was extracted three times with ethyl acetate and the combined organic layers were washed with 1M aqueous sodium hydroxide solution and brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by chromatography on silica gel (0.032–0.063 mm) with n-hexane as eluant to afford the desired product as a colorless oil (35.2%).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07098337B2uspto-grants-2006_08