Water → Methyl 2-(cis-3-hydroxycyclohexyloxymethyl)-6-methylbenzoate

5 g (42.8 mmol) of cis-1,3-cyclohexanediol were dissolved in 40 ml of chlorobenzene and 10 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU, dimethylpropyleneurea), admixed at 20–23° C. with 3.36 g (30 mmol) of potassium tert-butoxide (KOtBu) and stirred. After 10–15 minutes, the mixture was cooled to 15–20° C. and 3.7 g (approx. 50%) of methyl 2-bromomethyl-6-methylbenzoate were added dropwise. The mixture was stirred at 20° C. for 1.5 h and then added to water. The organic phase was removed and concentrated under reduced pressure. The residue was taken up in NMP/water and, to remove impurities, washed twice with n-heptane. Subsequently, the product was isolated by extracting twice with MTBE. The combined MTBE phases were washed with water, dried (Na2SO4) and concentrated under reduced pressure. The residue (1.2 g) was chromatographed on silica gel (1:1 ethyl acetate/n-heptane). 580 mg of the desired compound were obtained as a slightly 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. waitAfter 10–15 minutes
2. temperaturethe mixture was cooled to 15–20° C.
3. stirringThe mixture was stirred at 20° C. for 1.5 h
4. customThe organic phase was removed
5. concentrationconcentrated under reduced pressure
6. customto remove impurities
7. washwashed twice with n-heptane
8. customSubsequently, the product was isolated
9. extractionby extracting twice with MTBE
10. washThe combined MTBE phases were washed with water
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated under reduced pressure
13. customThe residue (1.2 g) was chromatographed on silica gel (1:1 ethyl acetate/n-heptane)

ORD record

ord-65ef42f140954425a031aa8adb08d3a5

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07094795B2