Propargyl bromide → (4R,9aR)-6-Cyclopropyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

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%).

1. temperaturewas heated
2. temperatureto reflux for 2 h
3. additionwas added
4. temperatureThe mixture was heated
5. temperatureto reflux for 16 h
6. temperaturethen cooled to room temperature
7. customthe phases were separated
8. extractionThe aqueous phase was extracted three times with ethyl acetate
9. washthe combined organic layers were washed with 1M aqueous sodium hydroxide solution and brine
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. customevaporated
13. customThe residue was purified by chromatography on silica gel (0.032–0.063 mm) with n-hexane as eluant

ORD-Eintrag

ord-90af6704e9c3417f9f4a191d574bb4d4

Quelldatensatz

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07098337B2