تفاعل #10479

معادلة التفاعل

water

potassium tert-butoxide

cis-1,3-cyclohexanediol

methyl 2-bromomethyl-6-methylbenzoate

→

desired compound

المردود 13.7%

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

المردود 13.7%

المذيبات

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

chlorobenzene

ظروف التفاعل

المعالجة

1. 1
   workup.WAITAfter 10–15 minutes
2. 2
   درجة الحرارةthe mixture was cooled to 15–20° C.
3. 3
   workup.STIRRINGThe mixture was stirred at 20° C. for 1.5 h
4. 4
   أخرىThe organic phase was removed
5. 5
   تركيزconcentrated under reduced pressure
6. 6
   أخرىto remove impurities
7. 7
   غسيلwashed twice with n-heptane
8. 8
   أخرىSubsequently, the product was isolated
9. 9
   استخلاصby extracting twice with MTBE
10. 10
    غسيلThe combined MTBE phases were washed with water
11. 11
    تجفيفdried (Na2SO4)
12. 12
    تركيزconcentrated under reduced pressure
13. 13
    أخرىThe residue (1.2 g) was chromatographed on silica gel (1:1 ethyl acetate/n-heptane)

الإجراء التجريبي

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).

المصدر