Dimethylformamide → cis-2-benzyl-3a-methyl-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]isoindole-6-carbaldehyde

HRID 1026644

反応式

HRID 1026644 の反応式
[CH2:1]([N:8]1[CH2:16][C@H:15]2[C@:10]([CH3:22])([CH2:11][CH2:12][C:13]3[C:20](Br)=[CH:19][CH:18]=[CH:17][C:14]=32)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[CH:30]=[O:31]>C1COCC1>[CH2:1]([N:8]1[CH2:16][C@H:15]2[C@:10]([CH3:22])([CH2:11][CH2:12][C:13]3[C:20]([CH:30]=[O:31])=[CH:19][CH:18]=[CH:17][C:14]=32)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 6228DimethylformamideHCID 70664398cis-2-benzyl-6-bromo-3a-methyl-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]isoindoleHCID 178418339Butyllithium

生成物 1

HCID 86670672cis-2-benzyl-3a-methyl-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]isoindole-6-carbaldehyde収率 55.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

cis-2-Benzyl-6-bromo-3a-methyl-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]isoindole (0.561 mmol, 200 mg) was dissolved in THF (5 ml) and the resulting solution was cooled to −78° C. Butyllithium (2.5 M in hexanes)(2.81 mmol, 1.123 ml) was added dropwise and the reaction mixture was stirred at −78° C. for 30 minutes. N,N-Dimethylformamide (8.42 mmol, 0.777 ml, 734 mg) was added and the reaction mixture was stirred at −78° C. for a further 2 h and then quenched by the addition of saturated aqueous ammonium chloride solution and allowed to warm to room temperature. The resulting biphasic solution was separated and the aqueous phase was further extracted with ether (2×). The combined organic extracts were dried over magnesium sulphate, filtered and the solvent removed in vacuo. The crude product was purified by silica column chromatography (eluting with heptane—50:50 EtOAc:Heptane) to afford cis-2-benzyl-3a-methyl-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]isoindole-6-carbaldehyde (95 mg), 1H NMR (400 MHz, CDCl3) ppm 10.29 (1H, s, CHO), 7.67-7.61 (1H, m, Ar—H), 3.62-3.55 (2H, m, NCH2Ph), 3.32-3.04 (4H, m, 4×CH), 2.73 (1H, d, CH), 2.49 (1H, d, CH), 2.30 (1H, t, CH), 1.88-1.78 (1H, m, CH), 1.53-1.45 (1H, m, CH), 1.20 (3H, s, CH3).

後処理

  1. stirringthe reaction mixture was stirred at −78° C. for a further 2 h
  2. customquenched by the addition of saturated aqueous ammonium chloride solution
  3. temperatureto warm to room temperature
  4. customThe resulting biphasic solution was separated
  5. extractionthe aqueous phase was further extracted with ether (2×)
  6. dry with materialThe combined organic extracts were dried over magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customThe crude product was purified by silica column chromatography (eluting with heptane—50:50 EtOAc:Heptane)

出典と根拠

ORDレコード
ord-6af45a59a2614a1caeabbf5f11401cd8
出典データセット
uspto-grants-2014_05
特許番号
US08729274B2

関連ノート

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