Hydrochloric Acid → Tert-butyl 2-(cis-3-hydroxycyclohexylmethoxy)-2-methylpropionate

温度

-78 °C

300 mg of tert-butyl (cis-3-methoxymethoxycyclohexylmethoxy)acetate are dissolved in 5 ml of abs. tetrahydrofuran and cooled to −78° C. (dry ice/acetone bath). 1.5 ml of a 2M lithium diisopropyl amide solution in tetrahydrofuran/hexane are then added dropwise. The solution is initially stirred at −78° C. for 90 min and then warmed to 0° C. (ice bath), 1.41 g of methyl iodide and 1.5 ml of tetrahydrofuran are added and the solution is stirred at 0° C. for 1 h. 1 ml of HCl (conc.) is added, and the phases are separated. The aqueous phase is extracted with ethyl acetate. The combined organic phases are dried over MgSO4 and concentrated (yield: 320 mg of crude product). The crude product is dissolved in 5 ml of abs. tetrahydrofuran and cooled to −78° C. (dry ice/acetone bath). 1.5 ml of a 2M lithium diisopropylamide solution in tetrahydrofuran/hexane are then added dropwise. The solution is initially stirred at −78° C. for 90 min and then warmed to 0° C. (ice bath), 1.41 g of methyl iodide and 1.5 ml of tetrahydrofuran are added and the solution is stirred at 0° C. for 1 h. 1 ml of HCl (conc.) is added, and the phases are separated. The aqueous phase is extracted with ethyl acetate. The combined organic phases are dried over MgSO4 and concentrated (yield: 350 mg of crude product). The residue is taken up in 1 ml of tetrahydrofuran, 1 ml of conc. HCl is added and the mixture is stirred at room temperature for 3 d. The mixture is diluted with water and ethyl acetate, the phases are separated and the aqueous phase is extracted with ethyl acetate. The combined organic phases are washed with saturated NaCl solution, dried over MgSO4 and concentrated. The residue is chromatographed on silica gel (heptane/ethyl acetate 2/1), giving 200 mg of tert-butyl 2-(cis-3-hydroxycyclohexylmethoxy)-2-methyl-propionate as a yellow oil. C15H28O4 (272.20), MS(ESI): 273.4 (MH+).

1. additionare added
2. stirringthe solution is stirred at 0° C. for 1 h
3. customthe phases are separated
4. extractionThe aqueous phase is extracted with ethyl acetate
5. dry with materialThe combined organic phases are dried over MgSO4
6. concentrationconcentrated (yield: 320 mg of crude product)
7. dissolutionThe crude product is dissolved in 5 ml of abs
8. temperaturetetrahydrofuran and cooled to −78° C. (dry ice/acetone bath)
9. addition1.5 ml of a 2M lithium diisopropylamide solution in tetrahydrofuran/hexane are then added dropwise
10. stirringThe solution is initially stirred at −78° C. for 90 min
11. temperaturewarmed to 0° C. (ice bath), 1.41 g of methyl iodide and 1.5 ml of tetrahydrofuran
12. additionare added
13. stirringthe solution is stirred at 0° C. for 1 h
14. addition1 ml of HCl (conc.) is added
15. customthe phases are separated
16. extractionThe aqueous phase is extracted with ethyl acetate
17. dry with materialThe combined organic phases are dried over MgSO4
18. concentrationconcentrated (yield: 350 mg of crude product)
19. addition1 ml of conc. HCl is added
20. stirringthe mixture is stirred at room temperature for 3 d
21. additionThe mixture is diluted with water and ethyl acetate
22. customthe phases are separated
23. extractionthe aqueous phase is extracted with ethyl acetate
24. washThe combined organic phases are washed with saturated NaCl solution
25. dry with materialdried over MgSO4
26. concentrationconcentrated
27. customThe residue is chromatographed on silica gel (heptane/ethyl acetate 2/1)

ORDレコード

ord-7b69e7eddb7c44778ab6e2f94562bc79

出典データセット

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07259177B2