반응 #83693

반응 방정식

2-methoxyphenylacetic acid

(3aRS,7SR,7aRS)-7-methyl-7-phenyl-4-perhydroisoindolone hydrochloride

triethylamine

→

(3aRS,7SR,7aRS)-7-methyl-7-phenyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone

수율 49.5%

용매

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   workup.ADDITIONis followed by dropwise addition of a solution
2. 2
   workup.STIRRINGAfter stirring for 2 hours
3. 3
   세척the reaction mixture is washed twice with 50 cm3 of water
4. 4
   기타The organic phase is separated out after settling
5. 5
   건조dried over magnesium sulphate
6. 6
   여과filtered
7. 7
   농축concentrated to dryness under reduced pressure (2.7 kPa)
8. 8
   기타The residue is chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 3 cm, height 15 cm)
9. 9
   세척eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (80/20 by volume)
10. 10
    기타collecting 50 cm3 fractions
11. 11
    농축concentrated to dryness under reduced pressure (2.5 kPa)
12. 12
    기타The residue is crystallized in 30 cm3 of ethyl acetate

실험 절차

To a solution of 1.66 g of 2-methoxyphenylacetic acid in 40 cm3 of dichloromethane are added, at 4° C., 1.62 g of N,N'-carbonyldiimidazole. Stirring for 30 minutes at room temperature is followed by dropwise addition of a solution containing 1.85 g of (3aRS,7SR,7aRS)-7-methyl-7-phenyl-4-perhydroisoindolone hydrochloride and 0.7 g of triethylamine in 30 cm3 of dichloromethane. After stirring for 2 hours, the reaction mixture is washed twice with 50 cm3 of water and then with 50 cm3 of saturated aqueous sodium chloride solution. The organic phase is separated out after settling has taken place, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 3 cm, height 15 cm), eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (80/20 by volume) and collecting 50 cm3 fractions. Fractions 16 to 60 are combined and then concentrated to dryness under reduced pressure (2.5 kPa). The residue is crystallized in 30 cm3 of ethyl acetate. 1.3 g of (3aRS,7SR,7aRS)-7-methyl-7-phenyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone are obtained, in the form of white crystals melting at 160° C.

출처