反应详情

A solution of isopropylmagnesium chloride [prepared by the reaction of magnesium (2.4 g) and 2-chloropropane (10 ml) in tetrahydrofuran (30 ml)] was added dropwise under argon at -20° C. to a solution of 3-chloropropan-1-ol (9.45 g) in tetrahydrofuran (100 ml). Magnesium (3.6 g) was added and the mixture was allowed to stand for twenty minutes and was then heated under reflux in the presence of 1,2-dibromopropane for 40 minutes. 1-(4-Chlorophenyl)cyclobutanecarbonitrile (8 g) was added and the mixture was heated under reflux for 16 hours. The mixture was cooled and the supernatant liquid decanted from excess magnesium metal and treated with sodium borohydride (3 g) and propan-2-ol (100 ml). The mixture was heated under reflux for 5 hours. The reaction mixture was cooled, added to water and excess concentrated hydrochloric acid was added. The resulting solution was washed with toluene, basified and extracted with toluene. The extracts were dried and evaporated to give a residue which was distilled in a Buchi Kugelrohr apparatus (140°/0.4 mm) to give 4-amino-4-[1-(4-chlorophenyl)-cyclobutyl]butan-1-ol.

1. waitto stand for twenty minutes
2. temperaturewas then heated
3. temperaturethe mixture was heated
4. temperatureunder reflux for 16 hours
5. temperatureThe mixture was cooled
6. customthe supernatant liquid decanted from excess magnesium metal
7. additiontreated with sodium borohydride (3 g) and propan-2-ol (100 ml)
8. temperatureThe mixture was heated
9. temperatureunder reflux for 5 hours
10. temperatureThe reaction mixture was cooled
11. additionadded to water and excess concentrated hydrochloric acid
12. additionwas added
13. washThe resulting solution was washed with toluene
14. extractionextracted with toluene
15. customThe extracts were dried
16. customevaporated
17. customto give a residue which
18. distillationwas distilled in a Buchi Kugelrohr apparatus (140°/0.4 mm)