反应详情

To a stirring solution of 3-pyrrolidin-1-ylmethyl-1-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutanol (Example 210, General procedure B, Step D) (0.10 g, 0.32 mmol) in 1,2-dichloroethane (3.2 mL) was added methanesulfonic acid (0.31 g, 3.2 mmol). The reaction was then heated to 65 □C (oil bath) for 30 minutes. The reaction was then cooled to room temperature and transferred to a Parr bottle. To this crude solution was added 5 mL of MeOH, 10% Pd/C (100 mg), and then the reaction vessel was pressurized to 45 psi with H2. After 30 min the reaction was purged with N2, filtered through a pad of celite, and concentrated under reduced pressure. Purification of this material was accomplished flash column chromatography using a 15 g ISCO column, pre-packing material on silica, eluting with a gradient of 20%–45% MeOH/CH2Cl2 with 0.1% NH4OH. The product containing fractions were collected and concentrated to give the title compound as the (0.97 mg) as the bis-methanesulfonic acid salt.

1. temperatureThe reaction was then heated to 65 □C (oil bath) for 30 minutes
2. customAfter 30 min the reaction was purged with N2
3. filtrationfiltered through a pad of celite
4. concentrationconcentrated under reduced pressure
5. customPurification of this material
6. washeluting with a gradient of 20%–45% MeOH/CH2Cl2 with 0.1% NH4OH
7. additionThe product containing fractions
8. customwere collected
9. concentrationconcentrated