Diisopropylethylamine → 2-[6-(4-Phenyl-1-Piperidinyl)Hexyl]-1H-Isoindole-1,3(2H)-Dione

HRID 2087156Notes

Reaction equation

Cl.[C:2]1([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]1[C:25](=[O:26])[C:24]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:23]2[C:22]1=[O:31].C(N(CC)C(C)C)(C)C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1>[C:2]1([CH:8]2[CH2:9][CH2:10][N:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]3[C:22](=[O:31])[C:23]4[C:24](=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:25]3=[O:26])[CH2:12][CH2:13]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To the 500 ml RB-flask was added 4-phenylpiperidine hydrochloride (5 g, 25 mmol), N-(6-bromohexyl)phthalimide (15.5 g, 50 mmol), N,N-diisopropylethylamine (21.8 ml, 125 mmol), tetrabutylammonium iodide (0.2 g), and dioxane (250 ml) at room temperature. The reaction mixture was stirred at 100° C. for 72 h. The solvent was removed in vacuo and the crude product was purified by flash chromatography (98:2=Chloroform:2N ammonia in methanol) to afford 7.67 g of the desired product (77% yield): 1H NMR (400 MHz, CDCl3) δ 7.78-7.79 (m, 2H), 7.74-7.65 (m, 2H), 7.32-7.14 (m, 5H), 3.69 (t, 2H, J=7.35 Hz), 3.06 (d, 2H, J=11.0 Hz), 2.49 (quintet, 1H, J=7.6 Hz), 2.36 (t, 2H, J=7.6 Hz), 2.02 (t, 2H, J=12.5 Hz), 1.82 (br s, 4H), 1.69 (t, 2H, J=6.3 Hz), 1.54 (br s, 2H), 1.37 (br s, 4H); ESMS m/e: 391.3 (M+H)+; Anal. Calc. for C25H30N2O2+0.2H2O: C, 76.19; H, 7.77; N, 7.11. Found: C, 76.14; H, 7.38; N, 7.13.

Workup

customThe solvent was removed in vacuo
customthe crude product was purified by flash chromatography (98:2=Chloroform:2N ammonia in methanol)

Sources & evidence

ORD record: ord-a605a03a82524ea28d8ea70032bac750
Source dataset: uspto-grants-2004_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06727264B1

Reaction notes

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