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

Temperature

5 °C

10.0 g (86 mmol) of cis-1,3-cyclohexanediol were taken up in 150 ml of methyl tert-butyl ether (MTBE), admixed at approx. 20° C. with 6.72 g (59.9 mmol) of potassium tert-butoxide (KOtBu) and stirred. After about 30 minutes, the suspension was cooled to 5° C. and admixed dropwise with 7.4 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. The mixture was stirred at 0–5° C. for 1 h, heated to 20–23° C. and left to stir overnight. Water was added, the mixture was stirred vigorously, the phases were separated, the organic phase was washed once more with water and then the organic phase was concentrated under reduced pressure. The residue (4.6 g) was chromatographed on silica gel (1:1 ethyl acetate/n-heptane). 1.2 g of the desired compound were 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), 1.82 (m, 1H), 2.05 (m, 1H), 2.34 (s, 3H), 3.46 (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. stirringThe mixture was stirred at 0–5° C. for 1 h
2. temperatureheated to 20–23° C.
3. waitleft
4. stirringto stir overnight
5. stirringthe mixture was stirred vigorously
6. customthe phases were separated
7. washthe organic phase was washed once more with water
8. concentrationthe organic phase was concentrated under reduced pressure
9. customThe residue (4.6 g) was chromatographed on silica gel (1:1 ethyl acetate/n-heptane)

ORD record

ord-34aac6db739c484d8d628fa15ea117fa

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07094795B2