반응 #10479

반응 방정식

water

potassium tert-butoxide

cis-1,3-cyclohexanediol

methyl 2-bromomethyl-6-methylbenzoate

→

desired compound

수율 13.7%

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

수율 13.7%

용매

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

chlorobenzene

반응 조건

후처리

1. 1
   workup.WAITAfter 10–15 minutes
2. 2
   온도the mixture was cooled to 15–20° C.
3. 3
   workup.STIRRINGThe mixture was stirred at 20° C. for 1.5 h
4. 4
   기타The organic phase was removed
5. 5
   농축concentrated under reduced pressure
6. 6
   기타to remove impurities
7. 7
   세척washed twice with n-heptane
8. 8
   기타Subsequently, the product was isolated
9. 9
   추출by extracting twice with MTBE
10. 10
    세척The combined MTBE phases were washed with water
11. 11
    건조dried (Na2SO4)
12. 12
    농축concentrated under reduced pressure
13. 13
    기타The residue (1.2 g) was chromatographed on silica gel (1:1 ethyl acetate/n-heptane)

실험 절차

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).

출처