2-Methoxyphenylacetic acid → (3aRS,7aRS)-7,7-Bis(3-fluorophenyl)-2-(phenylacetyl)perhydro-4-isoindolone

HRID 1029937ノート

反応式

HRID 1029937 の反応式
CO[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([OH:12])=O.Cl.[F:14][C:15]1[CH:16]=[C:17]([C:21]2([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=3)[CH:29]3[CH:25]([CH2:26][NH:27][CH2:28]3)[C:24](=[O:30])[CH2:23][CH2:22]2)[CH:18]=[CH:19][CH:20]=1.C(N(CC)CC)C>ClCCl>[F:37][C:33]1[CH:32]=[C:31]([C:21]2([C:17]3[CH:18]=[CH:19][CH:20]=[C:15]([F:14])[CH:16]=3)[CH:29]3[CH:25]([CH2:26][N:27]([C:10](=[O:12])[CH2:9][C:4]4[CH:3]=[CH:8][CH:7]=[CH:6][CH:5]=4)[CH2:28]3)[C:24](=[O:30])[CH2:23][CH2:22]2)[CH:36]=[CH:35][CH:34]=1

参加物

5

反応物 3

HCID 71342-Methoxyphenylacetic acidHCID 8471TriethylamineHCID 679158007,7-Bis(3-Fluorophenyl)-4-perhydroisoindolone hydrochloride

生成物 1

HCID 67916043(3aRS,7aRS)-7,7-Bis(3-fluorophenyl)-2-(phenylacetyl)perhydro-4-isoindolone収率 62.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

A solution of (2-methoxyphenyl)acetic acid (0.46 g) in dry dichloromethane (15 cc) is cooled to 0° C. and then treated with N,N'-carbonyldiimidazole (0.45 g) and stirred for 1 hour at 0° C. A solution of 7,7-bis-(3-fluorophenyl)-4-perhydroisoindolone hydrochloride (1 g) and triethylamine (0.76 cc) in dichloromethane (20 cc) is added dropwise. The reaction mixture is stirred for 3 hours at 25° C. and then washed with water (2×50 cc) and with saturated sodium chloride solution (50 cc). The organic phase is dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.04-0.063 mm, diameter 2.2 cm, height 23 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (70/30) and collecting 15 cc fractions. Fractions 4 to 9 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and the product obtained is recrystallized from acetonitrile. The crystals are drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-bis-(3-fluorophenyl)-2-(phenylacetyl)-4-perhydroisoindolone (0.76 g) is obtained. m.p.=194° C.

後処理

  1. stirringThe reaction mixture is stirred for 3 hours at 25° C.
  2. washwashed with water (2×50 cc) and with saturated sodium chloride solution (50 cc)
  3. dry with materialThe organic phase is dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed on a silica gel column (particle size 0.04-0.063 mm, diameter 2.2 cm, height 23 cm)
  7. washeluting under a nitrogen pressure of 0.5 bar
  8. additionwith a mixture of cyclohexane and ethyl acetate (70/30)
  9. customcollecting 15 cc fractions
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  11. customthe product obtained
  12. customis recrystallized from acetonitrile
  13. washwashed with isopropyl ether
  14. customdried

出典と根拠

ORDレコード
ord-3e8222c6b0754b30bc081b7840d01759
出典データセット
uspto-grants-1992_04
特許番号
US05102667

反応ノート

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