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

HRID 1026644

반응식

HRID 1026644 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-6af45a59a2614a1caeabbf5f11401cd8
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08729274B2

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