反应详情

229.3 g (3.5 mol) of zinc in 3.0 liters of dichloromethane are mixed with 230 ml of trimethylchlorosilane under nitrogen and stirred for 20 minutes at ambient temperature. Then 1.1 liters of absolute tetrahydrofuran are added and the mixture is heated to reflux temperature. To this mixture is added dropwise a mixture of 500 g (2.6 mol) of ethyl bromoisobutyrate (1) and 226.4 g (1.5 mol) of m-methoxybenzylcyanide (2) and the resulting mixture is then refluxed for 1.5 hours. It is allowed to cool, decanted off from the excess zinc and after cooling to about 10° C. mixed with 96.7 g (1.5 mol) of sodium cyanoborohydride. Then 300 ml of ethanol are slowly added dropwise (gas evolved). The reaction is allowed to continue for 20 minutes, 1.0 liters of conc. ammonia solution are added, the phases are separated and the organic phase is washed once more with a mixture of 500 ml of conc. ammonia solution and 500 ml of water. The organic phase is dried over sodium sulphate and evaporated down in vacuo. The residue is taken up in 2.3 liters of toluene and extracted twice with 1.8 liters of 2N hydrochloric acid. Then the aqueous phase is made alkaline with 700 ml of conc. ammonia solution and extracted twice with 2.2 liters of dichloromethane. After the organic phase has been dried over sodium sulphate it is evaporated down in vacuo. The ethyl 3-amino-4-(3-methoxyphenyl)-2-dimethylbutanoate (4) is isolated in a yield of 322.5 g (81% of theory) as a yellow oil.

1. temperaturethe mixture is heated
2. temperatureto reflux temperature
3. additionTo this mixture is added dropwise
4. temperaturethe resulting mixture is then refluxed for 1.5 hours
5. temperatureto cool
6. customdecanted off from the excess zinc
7. temperatureafter cooling to about 10° C.
8. waitto continue for 20 minutes
9. customthe phases are separated
10. washthe organic phase is washed once more with a mixture of 500 ml of conc. ammonia solution and 500 ml of water
11. dry with materialThe organic phase is dried over sodium sulphate
12. customevaporated down in vacuo
13. extractionextracted twice with 1.8 liters of 2N hydrochloric acid
14. extractionextracted twice with 2.2 liters of dichloromethane
15. dry with materialAfter the organic phase has been dried over sodium sulphate it
16. customis evaporated down in vacuo