Ammonium Chloride → Tert-butyl 2-(cis-3-hydroxycyclohexylmethoxy)pentanoate

Participants

Reaction Conditions

Reaction Steps

200 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). 0.7 ml of a 2M lithium diisopropylamide solution in tetrahydrofuran/hexane is then added dropwise. The solution is initially stirred at −78° C. and then warmed to 0° C. (ice bath) and stirred at this temperature for 20 min. 600 mg of propyl iodide in 2 ml of tetrahydrofuran are then added, and the solution is stirred at 0° C. for a further 2.5 h. 15 ml of a saturated ammonium chloride solution are added, and the phases are separated. The aqueous phase is extracted with methyl tert-butyl ether. The combined organic phases are dried over MgSO4 and concentrated (yield: 240 mg of crude product). The residue is taken up in 2 ml of tetrahydrofuran, 0.5 ml of conc. HCl is added and the mixture is stirred at room temperature for 18 h. The mixture is diluted with water and methyl tert-butyl ether, the phases are separated and the aqueous phase is extracted with methyl tert-butyl ether. The combined organic phases are washed with saturated NaCl solution, dried over MgSO4 and concentrated. This gives 130 mg of tert-butyl 2-(cis-3-hydroxycyclohexylmethoxy)-pentanoate as a yellow oil. NMR (CDCl3) diastereomer mixture: 3.55-3.67 (m, 2H), 3.41-3.48 (m, 1H), 3.07-3.18 (m, 1H), 1.91-2.13 (m, 2H), 1.11-1.82 (m, 14H), 1.48 (s, 9H).

Provenance & Evidence