反应详情

A cooled (0° C.) solution of 4-cyclopropylmethanesulfonyl-1-cyclopropylmethylcyclohex-3-enecarbonitrile (3.5 g, 12.4 mmol) in tetrahydrofuran (10 ml) was treated with borane tetrahydrofuran complex (1M in tetrahydrofuran, 62 ml) dropwise over 20 min. On complete addition the mixture was allowed to warm to ambient temperature and stirred for 4 hours. The solution was cooled to 0° C. and quenched by the slow addition onto cooled (0° C.) methanol (30 ml). On complete addition concentrated hydrochloric acid (3.5 ml) was added and the mixture was allowed to warm to ambient temperature and stirred for 1 hour. The solvent was evaporated and the residue azeotroped with toluene to give a white solid. The solid was dissolved in methanol:dichloromethane (1:1) and purified using an SCX cartridge. The product was washed with methanol then eluted with 2M ammonia in methanol and evaporated to give the desired product as a colourless oil (2.87 g, 81%). 1H NMR δ (ppm) (d6-DMSO): 3.21 (2H, s), 3.05-2.98 (3H, m), 2.62 (2H, s), 1.88-1.84 (2H, m), 1.80-1.74 (2H, m), 1.60-1.53 (2H, m), 1.28-1.22 (2H, m), 1.15 (2H, d, J=6.7 Hz), 1.10-1.02 (1H, m), 0.64-0.62 (3H, m), 0.43-0.36 (4H, m), 0.13-0.06 (2H, m).

1. additionOn complete addition the mixture
2. temperatureThe solution was cooled to 0° C.
3. customquenched by the slow addition
4. temperatureonto cooled (0° C.) methanol (30 ml)
5. additionOn complete addition concentrated hydrochloric acid (3.5 ml)
6. additionwas added
7. temperatureto warm to ambient temperature
8. stirringstirred for 1 hour
9. customThe solvent was evaporated
10. customthe residue azeotroped with toluene
11. customto give a white solid
12. custompurified
13. washThe product was washed with methanol
14. washthen eluted with 2M ammonia in methanol
15. customevaporated