Réaction #83673

Équation de réaction

ammonium chloride

(3aRS,6SR,7aSR)-2-benzyl-6-methyl-4-perhydroisoindolone

n-butyllithium

anisole

→

(3aRS,4RS,6SR,7aSR)-2-benzyl-4-(2methoxyphenyl)-6-methyl-4-perhydroisoindolol

Solvants

t-butyl methyl ether

tetramethylethylenediamine

tetrahydrofuran

hexane

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONare added at this temperature over thirty minutes
2. 2
   Températurethe reaction mixture is warmed to room temperature
3. 3
   Autredecanted
4. 4
   LavageThe organic phase is washed with water (3 times 150 cm3)
5. 5
   Séchagewith saturated sodium chloride solution (150 cm3), dried over magnesium sulphate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under reduced pressure (2.7 kPa)
8. 8
   AutreThe residue obtained
9. 9
   Autreis chromatographed on a column of silica gel (0.060-0.200 mm, diameter 6 cm, height 55 cm)
10. 10
    Lavageeluting under a pressure of 0.7 bar with a mixture of ethyl acetate and cyclohexane [by volume
11. 11
    Autre30/70 (3 dm3) then 50/50 (2 dm3) and 100/0 (3 dm3)] and collecting 200 cm3 fractions
12. 12
    Concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
13. 13
    Autrecrystallized in isopropyl ether

Mode opératoire

135 cm3 of 1.6M n-butyllithium solution in hexane are added to 31.3 cm3 of anisole diluted in 400 cm3 of t-butyl methyl ether and 33 cm3 of tetramethylethylenediamine, while maintaining the temperature below 30° C. After one hour at 20° C., the reaction mixture is cooled to -72° C. and 24 g of (3aRS,6SR,7aSR)-2-benzyl-6-methyl-4-perhydroisoindolone dissolved in 200 cm3 of tetrahydrofuran are added at this temperature over thirty minutes. After stirring for thirty minutes, 200 cm3 of aqueous 26% ammonium chloride solution are poured in over thirty minutes and the reaction mixture is warmed to room temperature and decanted. The organic phase is washed with water (3 times 150 cm3) and then with saturated sodium chloride solution (150 cm3), dried over magnesium sulphate, filtered and concentrated under reduced pressure (2.7 kPa). The residue obtained is chromatographed on a column of silica gel (0.060-0.200 mm, diameter 6 cm, height 55 cm), eluting under a pressure of 0.7 bar with a mixture of ethyl acetate and cyclohexane [by volume: 30/70 (3 dm3) then 50/50 (2 dm3) and 100/0 (3 dm3)] and collecting 200 cm3 fractions. Fractions 9 to 26 are combined, concentrated to dryness under reduced pressure (2.7 kPa) and crystallized in isopropyl ether. 20.5 g of (3aRS,4RS,6SR,7aSR)-2-benzyl-4-(2methoxyphenyl)-6-methyl-4-perhydroisoindolol are obtained in the form of white crystals, m.p.=120° C.

Source