Реакция #10479

Уравнение реакции

water

potassium tert-butoxide

cis-1,3-cyclohexanediol

methyl 2-bromomethyl-6-methylbenzoate

→

desired compound

Выход 13.7%

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

Выход 13.7%

Растворители

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

chlorobenzene

Условия реакции

Обработка

1. 1
   workup.WAITAfter 10–15 minutes
2. 2
   Температураthe mixture was cooled to 15–20° C.
3. 3
   workup.STIRRINGThe mixture was stirred at 20° C. for 1.5 h
4. 4
   ДругоеThe organic phase was removed
5. 5
   Концентрированиеconcentrated under reduced pressure
6. 6
   Другоеto remove impurities
7. 7
   Промывкаwashed twice with n-heptane
8. 8
   ДругоеSubsequently, the product was isolated
9. 9
   Экстракцияby extracting twice with MTBE
10. 10
    ПромывкаThe combined MTBE phases were washed with water
11. 11
    Сушкаdried (Na2SO4)
12. 12
    Концентрированиеconcentrated under reduced pressure
13. 13
    ДругоеThe residue (1.2 g) was chromatographed on silica gel (1:1 ethyl acetate/n-heptane)

Методика

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).

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