Water → 3-[(R*)-1-((S)-5-benzyloxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-piperidin-3-yl]-phenol

A mixture of hydrochloride salt of (R*)-3-(piperidin-3-yl)-phenol (240 mg, 1.12 mmol) and sodium bicarbonate in N,N-dimethylformamide (3 ml) were stirred at +120° C. under nitrogen atmosphere. To this mixture, a mixture of methanesulfonic acid (R)-5-benzyloxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl ester (390 mg, 1.11 mmol) in N,N-dimethylformamide (3 ml) was added, and stirred at +130° C. for 3.5 h. The reaction mixture was cooled down, water (20 ml) and ethyl acetate (15 ml) were added and the layers were separated. Organic phase was recovered and water layer was extracted twice with ethyl acetate. Organic phase and ethyl acetate extracts were combined and washed five times with water and saturated sodium chloride solution. The combined organic phase was dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified with flash chromatography using heptane and ethyl acetate as eluents to give 160 mg of the title compound.

1. additionwas added
2. stirringstirred at +130° C. for 3.5 h
3. temperatureThe reaction mixture was cooled down
4. customthe layers were separated
5. customOrganic phase was recovered
6. extractionwater layer was extracted twice with ethyl acetate
7. washwashed five times with water and saturated sodium chloride solution
8. dry with materialThe combined organic phase was dried (Na2SO4)
9. filtrationfiltered
10. customevaporated to dryness
11. customThe crude product was purified with flash chromatography

ORD 기록

ord-7997b99eff2a4b7c9a2f3c1370b173a7

출처 데이터셋

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08809536B2