反应详情

A solution of 3-chloropropan-1-ol (95 ml) in tetrahydrofuran cooled to below -5° C. was added over 30 minutes to a solution of isopropylmagnesium chloride [prepared from magnesium (30 g), 2-chloropropane (100 ml) and tetrahydrofuran (300 ml)]. Magnesium (36 g) was added and the mixture warmed to initiate the reaction which then had to be cooled. Tetrahydrofuran (300 ml) was then added and the mixture heated under reflux for 30 minutes. 1-(4-Chlorophenyl)cyclobutanecarbonitrile (90 g) was added and the mixture heated under reflux for 16 hours and then cooled. Sodium borohydride (30 g) and then propan-2-ol (250 ml) were added and the mixture heated under reflux for 5 hours. The reaction mixture was poured into water (1 l), and acidified with excess concentrated hydrochloric acid. The resulting acidic mixture was extracted with toluene. Removal of the toluene gave a residue which was triturated with ether to give a solid which was dried, basified and extracted with ether. The ether was removed by evaportion to give a residue which was distilled (180°/1 mm to 172°/0.8 mm) to give 4-amino-4-(1-(4-chlorophenyl)cyclobutyl]butan-1-ol.

1. temperaturethe mixture warmed
2. customthe reaction which
3. temperatureto be cooled
4. temperaturethe mixture heated
5. temperatureunder reflux for 30 minutes
6. temperaturethe mixture heated
7. temperatureunder reflux for 16 hours
8. temperaturecooled
9. temperaturethe mixture heated
10. temperatureunder reflux for 5 hours
11. extractionThe resulting acidic mixture was extracted with toluene
12. customRemoval of the toluene
13. customgave a residue which
14. customwas triturated with ether
15. customto give a solid which
16. customwas dried
17. extractionextracted with ether
18. customThe ether was removed by evaportion
19. customto give a residue which
20. distillationwas distilled (180°/1 mm to 172°/0.8 mm)