반응 #3713

반응 방정식

magnesium

(2RS,5SR)-2-dimethylaminomethyl-5-trifluoromethyl-cyclohexanone

3-trifluoromethyl-cyclohexanone

dimethylaminomethylene chloride

3-benzyloxy-1-bromobenzene

ammonium chloride

3-benzyloxy-1-bromobenzene

→

base ( 26 )

(1RS,2RS,5SR)-1-(3-benzyloxy-phenyl)-2-dimethylaminomethyl-5-trifluoromethyl-cyclohexanol

용매

tetrahydrofuran

tetrahydrofuran

acetonitrile

ether

tetrahydrofuran

반응 조건

후처리

1. 1
   온도the mixture was heated for one hour
2. 2
   온도under reflux
3. 3
   온도was thereafter cooled to 5°-10° C
4. 4
   workup.ADDITIONwere added at this temperature
5. 5
   온도was then cooled to 5°-10° C. again
6. 6
   기타the organic phase was separated off
7. 7
   추출the aqueous phase was extracted twice with 100 ml ether
8. 8
   건조The combined organic phases were dried over sodium sulphate
9. 9
   기타After removing the solvent
10. 10
    workup.DISTILLATIONby distillation
11. 11
    workup.ADDITIONthe residue (60.6 g) was introduced on to an 8×50 cm column
12. 12
    추출extracted with ethyl acetate/methanol

실험 절차

43.9 g (167 mmole) 3-benzyloxy-1-bromobenzene, dissolved in 200 ml of dry tetrahydrofuran, were added drop-wise to 4.06 g (167 mmole) magnesium turnings in 40 ml of dry tetrahydrofuran so that the reaction mixture boiled gently. After the addition of 3-benzyloxy-1-bromobenzene was complete, the mixture was heated for one hour under reflux and was thereafter cooled to 5°-10° C. 30.8 g (139 mmole) (2RS,5SR)-2-dimethylaminomethyl-5-trifluoromethyl-cyclohexanone, prepared from 3-trifluoromethyl-cyclohexanone and dimethylaminomethylene chloride in acetonitrile, dissolved in 80 ml of dry tetrahydrofuran, were added at this temperature. The reaction mixture was allowed to stand overnight and was then cooled to 5°-10° C. again. The Grignard solution was decomposed by the addition of 150 ml of 20% ammonium chloride solution. The reaction mixture was diluted with 200 ml of ether, the organic phase was separated off and the aqueous phase was extracted twice with 100 ml ether. The combined organic phases were dried over sodium sulphate. After removing the solvent by distillation, the residue (60.6 g) was introduced on to an 8×50 cm column packed with silica gel and extracted with ethyl acetate/methanol. 27.8 g (50% theoretical) of base (26) were obtained.

출처