반응 #12039

반응 방정식

triisobutylaluminium

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

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

intermediate b

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

1,2-dimethoxyethane

sodium hydroxide

triisobutylaluminium

→

desired compound

수율 76.2%

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

수율 76.2%

반응 조건

후처리

1. 1
   온도the reaction mixture was heated
2. 2
   온도under reflux for 66 h
3. 3
   workup.ADDITIONwas added
4. 4
   기타the reaction
5. 5
   온도again heated
6. 6
   온도under reflux
7. 7
   추출extracted three times with ethyl acetate
8. 8
   세척The combined organic layers were washed with brine
9. 9
   건조dried over magnesium sulfate
10. 10
    여과filtered
11. 11
    기타evaporated
12. 12
    기타The residue was chromatographed on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:3) as eluant

실험 절차

To a solution of 2.0 g (5.43 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) in 50 ml 1,2-dimethoxyethane 0.75 g (0.65 mmol) tetrakis(triphenylphosphine)palladium was added. After 20 min, 16.3 ml (16.3 mmol) triisobutylaluminium (1M solution in n-hexane) was added and the reaction mixture was heated under reflux for 66 h. After cooling to room temperature another 8.1 ml (8.1 mmol) triisobutylaluminium (1M solution in n-hexane) was added and the reaction again heated under reflux. After 5 h the reaction was poured onto 1M aqueous sodium hydroxide solution and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was chromatographed on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:3) as eluant to afford the desired compound as a light brown oil (76.2%).

출처