反应详情

1,1-Dimethylethyl 1-oxa-5-azaspiro[2.3]hexane-5-carboxylate (51 mg, 0.28 mmol) was taken into THF (1 mL) followed by addition of morpholine (123 μL, 1.4 mmol) and the mixture was stirred for one hour at room temperature. The solution was then concentrated and the residue partitioned with ethyl acetate and water. The organic layer was washed once with water then brine and the organic layer dried over anhydrous sodium sulfate. Filtration and concentration gave a colorless oil that was purified by silica gel flash chromatography using ethyl acetate to 10% methanol in dichloromethane as eluents. The combined pure fractions were concentrated and the residue treated with neat TFA (1 mL) for 5 minutes then concentrated. The residue was taken into methanol (2 mL) and basified to pH>10 by addition of Biorad AG-1× hydroxide form resin. Filtration and concentration afforded 3-(morpholin-4-ylmethyl)azetidin-3-ol (11.6 mg, 24% yield) as a colorless oil. 1H NMR (400 MHz, CD3OD): 3.69-3.66 (m, 4H), 3.55 (d, 2H), 3.49 (d, 2H), 2.66 (s, 2H), 2.57-2.55 (m, 4H).

1. concentrationThe solution was then concentrated
2. customthe residue partitioned with ethyl acetate and water
3. washThe organic layer was washed once with water
4. dry with materialbrine and the organic layer dried over anhydrous sodium sulfate
5. filtrationFiltration and concentration
6. customgave a colorless oil that
7. customwas purified by silica gel flash chromatography
8. concentrationThe combined pure fractions were concentrated
9. additionthe residue treated with neat TFA (1 mL) for 5 minutes
10. concentrationthen concentrated
11. additionbasified to pH>10 by addition of Biorad AG-1× hydroxide form resin
12. filtrationFiltration and concentration