反应详情

To a solution of compound 14 (0.907 g, 2.93 mmol) at 0 degrees in THF (3 mL) and under nitrogen was slowly added 1M borane tetrahydrofuran complex (11.73 mL, 11.73 mmol). The yellow solution was then stirred for 50 minutes at room temperature. It was cooled to 0 degrees and then slowly quenched with methanol (approx. 4 mL). After 10 minutes of stirring at room temperature the reaction solution was concentrated under reduced pressure to a yellow, gummy solid and dried under a high vacuum pump. The crude amine 5 was then dissolved in DCM (15 mL) at zero degrees and to this was added BOC-Ala-OSu (0.839 g, 2.93 mmol) followed by triethylamine (0.898 mL, 6.45 mmol). The reaction was stirred at zero degrees for 1 hour and at room temperature for 16 hours. The solvent was then removed under reduced pressure and the residue partitioned between ethyl acetate and saturated NH4Cl. The layers were separated and the ethyl acetate phase washed further with saturated NH4Cl and then brine, dried over Na2SO4, filtered and concentrated. The residue was absorbed onto silica gel and then purified by silica gel chromatography using a 40M Biotage column with a gradient of 20 to 60% ethyl acetate and hexanes to give compound 6 (0.718 g, 51%) as a white crusty solid. LRMS (ESI): calc. 484.1; found 385.1 (MH-Boc)+, 507.2 (MNa)+.

1. customat 0 degrees
2. temperatureIt was cooled to 0 degrees
3. customslowly quenched with methanol (approx. 4 mL)
4. stirringAfter 10 minutes of stirring at room temperature the reaction solution
5. concentrationwas concentrated under reduced pressure to a yellow, gummy solid
6. customdried under a high vacuum pump
7. dissolutionThe crude amine 5 was then dissolved in DCM (15 mL) at zero degrees
8. stirringThe reaction was stirred at zero degrees for 1 hour and at room temperature for 16 hours
9. customThe solvent was then removed under reduced pressure
10. customthe residue partitioned between ethyl acetate and saturated NH4Cl
11. customThe layers were separated
12. washthe ethyl acetate phase washed further with saturated NH4Cl
13. dry with materialbrine, dried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated
16. customThe residue was absorbed onto silica gel
17. custompurified by silica gel chromatography