反应详情

To a round bottom flask with stir bar was added (9H-fluoren-9-yl)methyl((2R,3S)-3-(tert-butoxy)-1-hydroxybutan-2-yl)carbamate (4.7 g, 12.3 mmol) and acetonitrile (100 mL) followed by the addition of piperidine (1.8 mL, 18.4 mmol). The flask was capped and stirred for 18 hr at room temperature. The volatiles were then removed. A white solid develops which contains the amino alcohol product and the fmoc deprotection by products. Solids were redissolved in acetonitrile (50 ml)(some of the fmoc polymer is insoluble) and 2,4-dichloropyrimidine (5.48 g, 36.8 mmol) and DIEA (2.141 mL, 12.26 mmol) were added. Resulting reaction mixture allowed to stir 18 hr at room temperature. The volatiles were again removed. Reaction mixture was diluted with water and extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 100%) provided (2R,3S)-3-(tert-butoxy)-2-((2-chloropyrimidin-4-yl)amino)butan-1-ol (1.80 g, 6.58 mmol, 54% yield) as a colorless oil which crystallizes upon standing. LCMS m/z 274.1 (M+H)+, Rt 0.56 min.

1. customThe flask was capped
2. stirringstirred for 18 hr at room temperature
3. customThe volatiles were then removed
4. dissolutionSolids were redissolved in acetonitrile (50 ml)(some of the fmoc polymer
5. additionwere added
6. customResulting
7. customreaction mixture
8. stirringto stir 18 hr at room temperature
9. customThe volatiles were again removed
10. customReaction mixture
11. extractionextracted with EtOAc
12. washwashed with water, brine
13. dry with materialdried (Na2SO4)
14. filtrationfiltered
15. concentrationconcentrated onto silica gel