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

Participants

Reaction Conditions

Reaction Steps

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+).

Provenance & Evidence