反应详情

温度

-70 °C

The crude N-(7-methyl-1,4-dioxaspiro[4.5]dec-8-ylidene)-1-phenylmethanamine was dissolved in MeOH (1.3 L). The solution was cooled to −70° C. and solid NaBH4 was added in ˜10 portions over 30 min while the reaction temperature was held below −64° C. The reaction mixture was allowed to warm to −30° C. over 1 h, then to 5° C. over 15 min. The reaction was quenched with water (500 mL), the mixture was transferred into a separatory funnel, additional water (2 L) was added (resulting pH 10-11), and extracted with CH2Cl2 (1 L+2×500 mL). The combined organics were dried (Na2SO4) and filtered through a pad of silica gel eluting with CH2Cl2 (200 mL). The filtrate was concentrated and the residue was solvent-switched with EtOH. The enantiomers of the trans-diastereomer were separated by preparative HPLC to afford the title compound.

1. customwas held below −64° C
2. temperatureto warm to −30° C. over 1 h
3. customThe reaction was quenched with water (500 mL)
4. customthe mixture was transferred into a separatory funnel
5. additionadditional water (2 L) was added
6. custom(resulting pH 10-11)
7. extractionextracted with CH2Cl2 (1 L+2×500 mL)
8. dry with materialThe combined organics were dried (Na2SO4)
9. filtrationfiltered through a pad of silica gel eluting with CH2Cl2 (200 mL)
10. concentrationThe filtrate was concentrated
11. customThe enantiomers of the trans-diastereomer were separated by preparative HPLC