Triphenylphosphine → 2-[[(2R)-4-[(3,4-Dichlorophenyl)methyl]morpholin-2-yl]methyl]isoindoline-1,3-dione

HRID 492119

反応式

HRID 492119 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[Cl:13])[CH2:5][NH:6][CH2:7][CH2:8][OH:9].O1C[C@@H]1[CH2:17][N:18]1[C:26](=[O:27])[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]1=[O:28].[C:29]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:30]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[Cl:13])[CH2:5][N:6]1[CH2:30][CH2:29][O:9][C@@H:8]([CH2:17][N:18]2[C:26](=[O:27])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]2=[O:28])[CH2:7]1

参加物

7

反応物 4

HCID 11776TriphenylphosphineHCID 2605252-[[(3,4-Dichlorophenyl)methyl]amino]ethanolHCID 719412(S)-(+)-N-(2,3-Epoxypropyl)phthalimideHCID 5363146Diisopropyl azodicarboxylate

生成物 1

HCID 450737512-[[(2R)-4-[(3,4-Dichlorophenyl)methyl]morpholin-2-yl]methyl]isoindoline-1,3-dione収率 71.5%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
105 °C

実験手順

A mixture of 2-[(3,4-dichlorobenzyl)amino]ethanol (400 g) and (S)-2-(oxiran-2-ylmethyl)-1H-isoindole-1,3(2H)-dione (399.6 g) in toluene (1150 ml) was stirred and heated at 103-107° C. under nitrogen. After 22.5 h the mixture was cooled to <60° C. and charged with tetrahydrofuran (2800 ml). Triphenyl phosphine (548 g) was added and the mixture was stirred until all the solid had dissolved, then cooled to 5-9° C. Diisopropylazodicarboxylate (412 ml) was then added over 70 min maintaining the temperature at <12°. The mixture was warmed to 21-25° and stirred for 1.5 h. The reaction mixture was concentrated by distillation to a final volume of 2800 ml. Methanol (2800 ml) was added and the concentration repeated to a volume of 2800 ml. More methanol (2000 ml) was added and the mixture was heated to 55°. After 0.75 h the slurry was cooled to 18° and then after a further 1 h the product was collected. The bed was washed with methanol (2×1200 ml) and then dried in vacuo at 40° to give the title compound (526.9 g).

後処理

  1. temperatureAfter 22.5 h the mixture was cooled to <60° C.
  2. stirringthe mixture was stirred until all the solid
  3. dissolutionhad dissolved
  4. temperaturecooled to 5-9° C
  5. temperaturemaintaining the temperature at <12°
  6. temperatureThe mixture was warmed to 21-25°
  7. stirringstirred for 1.5 h
  8. concentrationThe reaction mixture was concentrated by distillation to a final volume of 2800 ml
  9. additionMethanol (2800 ml) was added
  10. concentrationthe concentration
  11. additionMore methanol (2000 ml) was added
  12. temperaturethe mixture was heated to 55°
  13. temperatureAfter 0.75 h the slurry was cooled to 18°
  14. customafter a further 1 h the product was collected
  15. washThe bed was washed with methanol (2×1200 ml)
  16. customdried in vacuo at 40°

出典と根拠

ORDレコード
ord-8a896b15f8904a11acc8e63d6033e7ea
出典データセット
uspto-grants-2009_05
特許番号
US07531651B2

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