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

温度

5 °C

5 g (42.8 mmol) of cis-1,3-cyclohexanediol were dissolved in 50 ml of dimethoxyethane (DME), admixed at 20–23° C. with 3.36 g (30 mmol) of potassium tert-butoxide (KOtBu) and stirred. After about 30 minutes, the mixture is cooled to 5° C. and 3.7 g (approx. 50%) of methyl 2-bromomethyl-6-methylbenzoate, which may be prepared, for example, by methanolyzing the acid bromide (2-bromomethyl-6-methylbenzoyl bromide) or by brominating methyl 2,6-dimethylbenzoate, are added dropwise. The mixture is stirred at 5–10° C. for 1 h and then at 20–23° C. overnight. Water and methyl tert-butyl ether (MTBE) are added, the mixture is stirred vigorously, the phases are separated, the aqueous phase is washed once more with MTBE and the combined organic phases are concentrated under reduced pressure. The residue is chromatographed on silica gel (1:1 ethyl acetate/n-heptane). 600 mg of the desired compound are obtained as a light yellow oil, 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).

1. additionare added dropwise
2. stirringThe mixture is stirred at 5–10° C. for 1 h
3. customat 20–23° C.
4. customovernight
5. stirringthe mixture is stirred vigorously
6. customthe phases are separated
7. washthe aqueous phase is washed once more with MTBE
8. concentrationthe combined organic phases are concentrated under reduced pressure
9. customThe residue is chromatographed on silica gel (1:1 ethyl acetate/n-heptane)

ORDレコード

ord-39f6c4bd24b6470583618751582d3aed

出典データセット

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07094795B2