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

HRID 1026644

Reaction equation

[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

Participants

Conditions

Temperature: -78 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-6af45a59a2614a1caeabbf5f11401cd8
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729274B2

Linked notes

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