Hydrochloric Acid → (3aR, 7S, 7aR)-7-chloro-2-[(2-dimethylaminophenyl)acetyl]-4,4-diphenylperhydroisoindole hydrochloride

0.39 g of carbonyldiimidazole is added to a solution, cooled to +4° C., of 0.43 g of (2-dimethylaminophenyl)acetic acid in 15 cm3 of dry dichloromethane. The mixture is stirred for one hour at +4° C. and then a solution of 0.84 g of (3aR, 7S, 7aR)-7-chloro-4,4-diphenylperhydroisoindole hydrochloride in 10 cm3 of dry dichloromethane is added followed by a solution of 0.34 cm3 of triethylamine in 10 cm3 of dry dichloromethane. The reaction mixture is stirred at room temperature for 20 hours, and then diluted with 100 cm3 of dichloromethane, washed with 50 cm3 of water and then with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 23 cm), eluting under a nitrogen pressure of 0.4 bar with an ethyl acetate and cyclohexane mixture (25/75 by volume) and collecting fractions of 80 cm3. Fraction 2 is concentrated to dryness under reduced pressure (2.7 kPa). The product which is obtained in the form of a base is converted to the hydrochloride by dissolving in 4 cm3 of acetonitrile, followed by the addition of 6 cm3 of a 3.2N solution of hydrochloric acid in ethyl ether, washing with isopropyl ether and drying. 0.08 g of (3aR, 7S, 7aR)-7-chloro-2-[(2-dimethylaminophenyl)acetyl]-4,4-diphenylperhydroisoindole hydrochloride is obtained in the form of a beige solid.

1. stirringThe reaction mixture is stirred at room temperature for 20 hours
2. washwashed with 50 cm3 of water
3. dry with materialwith a saturated aqueous solution of sodium chloride, dried over magnesium sulphate
4. filtrationfiltered
5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
6. customThe residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 23 cm)
7. washeluting under a nitrogen pressure of 0.4 bar with an ethyl acetate and cyclohexane mixture (25/75 by volume)
8. customcollecting fractions of 80 cm3
9. concentrationFraction 2 is concentrated to dryness under reduced pressure (2.7 kPa)
10. customThe product which is obtained in the form of a base
11. washwashing with isopropyl ether
12. customdrying

ORDレコード

ord-389c0bc808da43be8162d375cf21b265

出典データセット

uspto-grants-1996_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05508433