Acetic Anhydride → 7-Bromo-2,3-dihydro-1H-inden-1-ol

온도

-20 °C

To a mixture of 100 g (746 mmol) of indan-1-ol, 250 ml (1.64 mol) of N,N,N′,N′-tetramethylethylenediamine, and 3000 ml of pentane cooled to −20° C. 655 ml (1.64 mol) of 2.5M nBuLi in hexanes was added. After that the reaction mixture was refluxed for 12 h and then cooled to −80° C. Further on, 225 ml (1.87 mol) of 1,2-dibromotetrafluoroethane was added, and the resulting mixture was allowed to warm to room temperature. This mixture was stirred for 12 h, and then 100 ml of water was added. The resulting mixture was diluted with 2000 ml of water, and the organic layer was separated. The aqueous layer was extracted with 3×400 ml of toluene. The combined organic extract was dried over Na2SO4 and evaporated to dryness. The residue was distilled using a Kugelrohr apparatus, b.p. 120-140° C./1 mbar. The resulting yellow oil was dissolved in 50 ml of triethylamine, and the obtained solution added dropwise to a stirred solution of 49.0 ml (519 mmol) of acetic anhydride and 4.21 g (34.5 mmol) of 4-(dimethylamino)pyridine in 70 ml of triethylamine. The resulting mixture was stirred for 5 min, then 1000 ml of water was added, and stirring was continued for 12 h. After that the reaction mixture was extracted with 3×200 ml of ethyl acetate. The combined organic extract was washed with aqueous Na2CO3, dried over Na2SO4, and evaporated to dryness. The residue was purified by flash chromatography on silica gel 60 (40-63 um, eluent: hexane-ethyl acetate=30:1, vol.). The resulting ester was dissolved in 1000 ml of methanol, 50.5 g (900 mmol) of KOH was added, and this mixture was refluxed for 3 h. The reaction mixture was then cooled to room temperature and poured into 4000 ml of water. Crude product was extracted with 3×300 ml of dichloromethane. The combined organic extract was dried over Na2SO4 and evaporated to dryness. Yield 41.3 g (26%) of a white crystalline solid. Anal. Calc for C9H9BrO: C, 50.73; H, 4.26. Found: C, 50.85; H, 4.48. 1H NMR (CDCl3): δ 7.34 (d, J=7.6 Hz, 1H, 6-H); 7.19 (d, J=7.4 Hz, 1H, 4-H); 7.12 (dd, J=7.6 Hz, J=7.4 Hz, 1H, 5-H); 5.33 (dd, J=2.6 Hz, J=6.9 Hz, 1H, 1-H), 3.18-3.26 (m, 1H, 3- or 3′-H), 3.09 (m, 2H, 3,3′-H); 2.73 (m, 2H, 2,2′-H).

1. temperatureAfter that the reaction mixture was refluxed for 12 h
2. temperaturecooled to −80° C
3. temperatureto warm to room temperature
4. customthe organic layer was separated
5. extractionThe aqueous layer was extracted with 3×400 ml of toluene
6. extractionThe combined organic extract
7. dry with materialwas dried over Na2SO4
8. customevaporated to dryness
9. distillationThe residue was distilled
10. dissolutionThe resulting yellow oil was dissolved in 50 ml of triethylamine
11. stirringThe resulting mixture was stirred for 5 min
12. stirringstirring
13. waitwas continued for 12 h
14. extractionAfter that the reaction mixture was extracted with 3×200 ml of ethyl acetate
15. extractionThe combined organic extract
16. washwas washed with aqueous Na2CO3
17. dry with materialdried over Na2SO4
18. customevaporated to dryness
19. customThe residue was purified by flash chromatography on silica gel 60 (40-63 um, eluent: hexane-ethyl acetate=30:1, vol.)
20. dissolutionThe resulting ester was dissolved in 1000 ml of methanol
21. temperaturethis mixture was refluxed for 3 h
22. temperatureThe reaction mixture was then cooled to room temperature
23. extractionCrude product was extracted with 3×300 ml of dichloromethane
24. extractionThe combined organic extract
25. dry with materialwas dried over Na2SO4
26. customevaporated to dryness

ORD 기록

ord-9b123ebc783f40ed8719d3a3c979ef77

출처 데이터셋

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09290519B2