Reaktion #10479

Reaktionsgleichung

water

potassium tert-butoxide

cis-1,3-cyclohexanediol

methyl 2-bromomethyl-6-methylbenzoate

→

desired compound

Ausbeute 13.7%

racemic methyl cis-2-(3-hydroxycyclohexyloxymethyl)-6-methylbenzoate

Ausbeute 13.7%

Lösungsmittel

1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone

chlorobenzene

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter 10–15 minutes
2. 2
   Temperaturthe mixture was cooled to 15–20° C.
3. 3
   workup.STIRRINGThe mixture was stirred at 20° C. for 1.5 h
4. 4
   SonstigeThe organic phase was removed
5. 5
   Einengenconcentrated under reduced pressure
6. 6
   Sonstigeto remove impurities
7. 7
   Waschenwashed twice with n-heptane
8. 8
   SonstigeSubsequently, the product was isolated
9. 9
   Extraktionby extracting twice with MTBE
10. 10
    WaschenThe combined MTBE phases were washed with water
11. 11
    Trocknendried (Na2SO4)
12. 12
    Einengenconcentrated under reduced pressure
13. 13
    SonstigeThe residue (1.2 g) was chromatographed on silica gel (1:1 ethyl acetate/n-heptane)

Vorschrift

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).

Quelle