반응 #12014

ord-90af6704e9c3417f9f4a191d574bb4d4

반응 방정식

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
수율 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
수율 35.2%

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도was heated
  2. 2
    온도to reflux for 2 h
  3. 3
    workup.ADDITIONwas added
  4. 4
    온도The mixture was heated
  5. 5
    온도to reflux for 16 h
  6. 6
    온도then cooled to room temperature
  7. 7
    기타the phases were separated
  8. 8
    추출The aqueous phase was extracted three times with ethyl acetate
  9. 9
    세척the combined organic layers were washed with 1M aqueous sodium hydroxide solution and brine
  10. 10
    건조dried over magnesium sulfate
  11. 11
    여과filtered
  12. 12
    기타evaporated
  13. 13
    기타The residue was purified by chromatography on silica gel (0.032–0.063 mm) with n-hexane as eluant

실험 절차

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%).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07098337B2uspto-grants-2006_08