Reaction #12051

Reaction equation

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

tert-butyllithium

5-chloro-2-pentanone

→

compound

Yield 50.9%

(4R,9aR)-6-(4-Chloro-1-(RS)-hydroxy-1-methyl-butyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

Yield 50.9%

Solvents

diethyl ether

Conditions

Workup

1. 1
   Otherto rise to −75 deg C
2. 2
   workup.WAITand after an additional 15 min
3. 3
   Otherthe reaction was quenched with 10%
4. 4
   Extractionaqueous ammonium chloride solution and extracted with ethyl acetate
5. 5
   WashThe organic layer was washed with brine
6. 6
   Dryingdried over magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   OtherThe solvent was removed on a rotary evaporator
9. 9
   Otherthe residue was chromatographed on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:2) as eluant

Procedure

A solution of 0.30 g (0.81 mmol) (4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester in 20 ml diethyl ether was cooled to −100 deg C. and treated dropwise with 65 μl (0.97 mmol) tert-butyllithium (1.5 M solution in n-pentane). After 15 min, 0.12 g (0.11 ml, 0.98 mmol) 5-chloro-2-pentanone was added, the temperature was allowed to rise to −75 deg C. and after an additional 15 min, the reaction was quenched with 10%. aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The solvent was removed on a rotary evaporator and the residue was chromatographed on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:2) as eluant to afford the compound as a colorless oil (50.9%).

Source