反応 #83682

反応方程式

ammonium chloride

(3aRS,7aRS)-7,7-dimethyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone

2-methoxyphenylmagnesium bromide

cerium chloride

→

(3aRS,4RS,7aRS)-7,7-dimethyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolol

収率 10.1%

溶媒

tetrahydrofuran

ethyl acetate

tetrahydrofuran

反応条件

後処理

1. 1
   workup.ADDITIONis added
2. 2
   workup.STIRRINGThe reaction mixture is stirred at room temperature for 18 hours
3. 3
   洗浄washed with 100 cm3 of saturated aqueous sodium chloride solution
4. 4
   その他The organic phase is separated out after settling
5. 5
   乾燥dried over magnesium sulphate
6. 6
   ろ過filtered
7. 7
   濃縮concentrated to dryness under reduced pressure (2.7 kPa)
8. 8
   その他The residue is chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 3.6 cm, height 22 cm)
9. 9
   洗浄eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (70/30 by volume)
10. 10
    その他collecting 50 cm3 fractions
11. 11
    濃縮concentrated to dryness under reduced pressure (2.5 kPa)
12. 12
    その他The residue is crystallized in 1 cm3 of acetonitrile

実験手順

To a suspension of 2.61 g of 2-methoxyphenylmagnesium bromide in 10 cm3 of tetrahydrofuran, cooled to 15° C., is added, dropwise and with stirring, a solution of 1.3 g of (3aRS,7aRS)-7,7-dimethyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone in 30 cm3 of tetrahydrofuran, followed by 2 g of anhydrous cerium chloride. The reaction mixture is stirred at room temperature for 18 hours, treated with 80 cm3 of saturated aqueous ammonium chloride solution, taken up in 100 cm3 of ethyl acetate and washed with 100 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 3.6 cm, height 22 cm), eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (70/30 by volume) and collecting 50 cm3 fractions. Fractions 47 to 54 are combined and then concentrated to dryness under reduced pressure (2.5 kPa). The residue is crystallized in 1 cm3 of acetonitrile. 0.177 g of (3aRS,4RS,7aRS)-7,7-dimethyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolol is obtained, in the form of white crystals melting at 187° C.

出典