反应详情

温度

60 °C

To a 250 mL RBF was added N-allyl-N-t-butylcarbamate-(4′S)-6′-(1-hydroxy-2,2-dimethylpropyl)-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-b]pyridin]-4′-amine (4.01 g, 9.6 mmol), toluene (100 mL), a dry ice bath, and after cooling for 20 minutes DAST (1.81 ml, 14 mmol) was added. After 1 hour, LC-MS shows Reactant 1 consumed. The reaction was quenched with sat'd NH4Cl (20 mL). The layers were separated and the aqueous layer extracted with EtOAc (20 mL). The combined organic layers were concentrated in vacuo to give a golden oil. The oil was taken up in MeOH (50 mL) and treated with HCl, 4M in dioxane (5.0 ml, 20 mmol). After 1.5 hours, no changes were seen by LC-MS. The reaction was treated with an additional HCl (5 mL) and heated to 60° C. After stirring for 5 hours, the solution was allowed to cool to RT. After a further 16 hours, the reaction was concentrated in vacuo to give a brown oil, which was taken up in DCM and washed with sat'd NaHCO3, brine and concentrated in vacuo to give N-allyl-(4′S)-6′-(1-fluoro-2,2-dimethylpropyl)-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-b]pyridin]-4′-amine (3.15 g) as a brown oil. MS m/z: 319 (M+1). The crude material was used without further purification in the next step.

1. additionwas added
2. customconsumed
3. customThe reaction was quenched with sat'd NH4Cl (20 mL)
4. customThe layers were separated
5. extractionthe aqueous layer extracted with EtOAc (20 mL)
6. concentrationThe combined organic layers were concentrated in vacuo
7. customto give a golden oil
8. waitAfter 1.5 hours
9. temperatureto cool to RT
10. waitAfter a further 16 hours
11. concentrationthe reaction was concentrated in vacuo
12. customto give a brown oil, which
13. washwashed with sat'd NaHCO3, brine
14. concentrationconcentrated in vacuo