Reaction #83691

Reaction equation

(3aRS,4RS,5RS,7aRS)-7,7-dimethyl-4-(2-methoxyphenyl)-4,5-perhydroisoindolediol

3-indoleacetic acid

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

diisopropylethylamine

→

(3aRS,4RS,5RS,7aRS)-7,7-dimethyl-4-(2-methoxyphenyl)-2-[(3-indolyl)acetyl]-4,5-perhydroisoindolediol

Yield 70.9%

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   Washthe organic phase is washed with 50 cm3 of aqueous sodium bicarbonate solution and with 60 cm3 of saturated aqueous sodium chloride solution
2. 2
   Dryingdried over magnesium sulphate
3. 3
   Concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
4. 4
   OtherThe cream-coloured foam obtained
5. 5
   Otheris chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 1 cm, height 30 cm)
6. 6
   Washeluting under a pressure of 0.5 bar nitrogen with a mixture of dichloromethane and methanol (97/3 by volume)
7. 7
   Othercollecting 30 cm3 fractions
8. 8
   Concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
9. 9
   Otherthe solid obtained
10. 10
    Otheris recrystallized in 5 cm3 of isopropyl ether

Procedure

To a solution of 0.44 g of (3aRS,4RS,5RS,7aRS)-7,7-dimethyl-4-(2-methoxyphenyl)-4,5-perhydroisoindolediol and 0.29 g of 3-indoleacetic acid in 40 cm3 of dichloromethane, cooled to 0° C., are added 5 mg of 1-hydroxybenzotriazole, 0.35 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.42 cm3 of diisopropylethylamine. The mixture is stirred for 15 hours at room temperature, 100 cm3 of dichloromethane are added and the organic phase is washed with 50 cm3 of aqueous sodium bicarbonate solution and with 60 cm3 of saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The cream-coloured foam obtained is chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 1 cm, height 30 cm), eluting under a pressure of 0.5 bar nitrogen with a mixture of dichloromethane and methanol (97/3 by volume) and collecting 30 cm3 fractions. Fractions 5 to 7 are combined and then concentrated to dryness under reduced pressure (2.7 kPa); the solid obtained is recrystallized in 5 cm3 of isopropyl ether. 0.48 g of (3aRS,4RS,5RS,7aRS)-7,7-dimethyl-4-(2-methoxyphenyl)-2-[(3-indolyl)acetyl]-4,5-perhydroisoindolediol is obtained, melting at 160-165° C.

Source