Methyl 2,6-dimethylbenzoate → Methyl 2-(cis-3-hydroxycyclohexyloxymethyl)-6-methylbenzoate

Participants

Reaction Conditions

Reaction Steps

500 g (4.3 mol) of cis-1,3-cyclohexanediol were dissolved in 5 l of NMP and admixed with 336 g (3.0 mol) of potassium tert-butoxide (KOtBu). The internal temperature rose to 28° C. The mixture was stirred for 30 min, then cooled to −5° C. and admixed dropwise with 370 g (approx. 94%, approx. 1.4 mol) of methyl 2-bromomethyl-6-methylbenzoate which may be prepared, for example, by methanolyzing 2-bromomethyl-6-methylbenzoyl bromide or by brominating methyl 2,6-dimethylbenzoate. The mixture was stirred for 30 min and then diluted with 5 l of water. After washing three times with 3 l of n-heptane each time and discarding the n-heptane solutions, the remaining aqueous phase was extracted four times with 2.5 l of MTBE each time. The combined MTBE phases were washed once with 5 l of water, dried over Na2SO4 and subsequently concentrated by evaporation under reduced pressure. 234 g of the desired compound were obtained as a yellowish oil and were used in the next reaction (for example an optical resolution) without further purification; 1H NMR (CDCl3), δ =1.27 (m, 1H), 1.45 (m, 1H), 1.55 (m, 1H), 1.74 (m, 1H), 1.83 (m, 1H), 2.05 (m, 1H), 2.34 (s, 3H), 3.47 (m, 1H), 3.72 (m, 1H), 3.91 (s, 3H), 4.58 (dd, 2H), 7.15 (d, 1H), 7.20 (d, 2H), 7.27 (m, 1H).

Provenance & Evidence