반응 #83711

반응 방정식

hydrochloric acid

(3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-6-methyl-4-perhydroisoindolol

(2-dimethylaminophenyl)acetic acid

1-hydroxybenzotriazole monohydrate

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

→

(3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisoindolol hydrochloride

수율 61.2%

용매

dioxane

dioxane

dichloromethane

triethylamine

반응 조건

후처리

1. 1
   온도The reaction mixture is maintained at 5° C. for 1 hour and at 20° C. for 16 hours
2. 2
   세척is then washed twice with 100 cm3 of water
3. 3
   건조dried over magnesium sulphate
4. 4
   여과filtered
5. 5
   농축concentrated under reduced pressure (2.7 kPa)
6. 6
   기타The residue is chromatographed on a column of silica gel (0.060-0.200 mm, diameter 4 cm, height 50 cm)
7. 7
   세척eluting under a pressure of 0.7 bar with a mixture of dichloromethane and methanol (97/3 by volume)
8. 8
   기타collecting 50 cm3 fractions
9. 9
   농축Fractions 14 to 19 are concentrated
10. 10
    기타after drying at 40° C. and at 15 Pa
11. 11
    기타1.0 g of (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisonindolol is obtained, in the form of a white powder which
12. 12
    농축the solution is concentrated under reduced pressure (2.7 kPa)
13. 13
    여과filtered
14. 14
    기타dried at 40° C. under 15 Pa

실험 절차

To a solution of 1.0 g of (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-6-methyl-4-perhydroisoindolol in 100 cm3 of dichloromethane are added 1.5 cm3 of triethylamine. The reaction mixture is cooled to 5° C. and 0.60 g of (2-dimethylaminophenyl)acetic acid, 0.10 g of 1-hydroxybenzotriazole monohydrate and 0.70 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are added. The reaction mixture is maintained at 5° C. for 1 hour and at 20° C. for 16 hours and is then washed twice with 100 cm3 of water, dried over magnesium sulphate, filtered and concentrated under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (0.060-0.200 mm, diameter 4 cm, height 50 cm), eluting under a pressure of 0.7 bar with a mixture of dichloromethane and methanol (97/3 by volume) and collecting 50 cm3 fractions. Fractions 14 to 19 are concentrated and, after drying at 40° C. and at 15 Pa, 1.0 g of (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisonindolol is obtained, in the form of a white powder which is dissolved in 50 cm3 of dioxane. 3 cm3 of 5M hydrochloric acid solution are added to the dioxane and, after 1 hour at room temperature, the solution is concentrated under reduced pressure (2.7 kPa), stirred in isopropyl ether, filtered and dried at 40° C. under 15 Pa. 0.94 g of (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisoindolol hydrochloride is obtained.

출처