反应详情

To a solution of 14.3 ml (0.1 mole) of diisopropylamine in 170 ml dry tetrahydrofuran is added dropwise 37 ml (93 mmol) of a 2.5M solution of n-butyllithium in hexane. The solution is stirred for 15 min and then a solution of 13.86 g (46.1 mmol) of 4-(4-t-butyldimethylsilyloxybutyl)-epsilon-caprolactone in 68 ml dry tetrahydrofuran is added slowly. The yellow solution is stirred at room temperature for 0.5 h and 19 ml (0.3 mole) methyl iodide is added rapidly. The exothermic reaction is controlled by cooling in a water bath. The reaction mixture is stirred for 3 h and quenched using saturated aqueous ammonium chloride solution. The mixture is extracted with ether and the organic layer is washed with water and brine. The organic phase is dried, filtered, concentrated and purified by chromatography using 3:2 hexane/ether as eluent to yield 2-methyl-4-(4-t-butyldimethylsilyloxybutyl)-epsilon-caprolactone; NMR (CDCl3): delta 4-4.4 (m,2H), 3.6 (t,2H), 1.2 (d,3H), 0.88 (s,9H). This is converted to methyl 8-amino-2-methyl-4-[3-(3-pyridyl)propyl]-octanoate in a similar fashion as described below for the 2,2-dimethyl analog.

1. stirringThe yellow solution is stirred at room temperature for 0.5 h
2. customThe exothermic reaction
3. temperatureby cooling in a water bath
4. stirringThe reaction mixture is stirred for 3 h
5. customquenched
6. extractionThe mixture is extracted with ether
7. washthe organic layer is washed with water and brine
8. customThe organic phase is dried
9. filtrationfiltered
10. concentrationconcentrated
11. custompurified by chromatography