反应详情

N,N'-Carbonyldiimidazole (1.14 g) is added to a solution of 2-fluorophenylacetic acid (1.08 g) in dry dichloromethane (30 cc) cooled to +5° C. The mixture is stirred for 20 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (2.3 g) and triethylamine (1.98 cc) in dichloromethane (20 cc) is then added. The reaction mixture is stirred at 20° C. for 72 hours and then washed with water (2×150 cc), dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The solid obtained is crystallized from a mixture of acetonitrile (30 cc) and isopropyl ether (50 cc). The crystals are drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-diphenyl-2-[(2-fluorophenyl)acetyl]-4-perhydroisoindolone (1.53 g) is obtained in the form of white crystals melting at 186° C.

1. temperaturecooled to +5° C
2. stirringThe reaction mixture is stirred at 20° C. for 72 hours
3. washwashed with water (2×150 cc)
4. dry with materialdried over magnesium sulphate
5. filtrationfiltered
6. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
7. customThe solid obtained
8. customis crystallized from a mixture of acetonitrile (30 cc) and isopropyl ether (50 cc)
9. washwashed with isopropyl ether
10. customdried