Tetrahydrofuran → 13-ethyl-8-isopropenyl-9,10-dimethoxy-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline

HRID 2381200Notes

Reaction equation

HRID 2381200 reaction equation
[CH2:1]([C:3]1[C:4]2[CH:5]=[CH:6][C:7]([O:26][CH3:27])=[C:8]([O:24][CH3:25])[C:9]=2[CH2:10][NH+:11]2[CH2:20][CH2:19][C:18]3[C:13](=[CH:14][C:15]4[O:23][CH2:22][O:21][C:16]=4[CH:17]=3)[C:12]=12)[CH3:2].[I-].[C:29]([Mg]Br)([CH3:31])=[CH2:30].O1CCCC1>C(OCC)C>[CH2:1]([C:3]1[C:4]2[CH:5]=[CH:6][C:7]([O:26][CH3:27])=[C:8]([O:24][CH3:25])[C:9]=2[CH:10]([C:29]([CH3:31])=[CH2:30])[N:11]2[CH2:20][CH2:19][C:18]3[C:13](=[CH:14][C:15]4[O:23][CH2:22][O:21][C:16]=4[CH:17]=3)[C:12]=12)[CH3:2]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 30165Iodide IonHCID 8664749213-Ethyl-9,10-dimethoxy-5,6-dihydro-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-yliumHCID 178456138HCID 178456138, compound

Product 1

HCID 4980609313-ethyl-8-isopropenyl-9,10-dimethoxy-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolineYield 12%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 13-ethyl-9,10-dimethoxy-5,6-dihydro-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ylium; iodide (300 mg, 0.61 mmol) in anhydrous diethyl ether (100 mL) at 0° C. was added a solution of isopropenylmagnesium bromide in tetrahydrofuran (0.5 M, 18.4 mL, 9.2 mmol) dropwise. After stirring at 0° C. for 30 min, the reaction was quenched by adding saturated aqueous ammonium chloride solution (20 mL). The mixture was extracted with diethyl ether (2×50 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was re-crystallized from diethyl ether to afford 13-ethyl-8-isopropenyl-9,10-dimethoxy-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline (32 mg, 12%). LC/MS m/e calcd for C25H27NO4 (M+H)+: 406.50, observed: 406.2; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16 (t, J=7.20 Hz, 3 H) 1.53 (s, 3 H) 2.57-2.64 (m, 1 H) 2.64-2.71 (m, 1 H) 2.64-2.71 (m, 1 H) 2.71-2.78 (m, 1 H) 2.95-3.04 (m, 1 H) 3.15-3.22 (m, 1 H) 3.72 (s, 3 H) 3.81 (s, 3 H) 4.60 (s, 1 H) 4.72 (s, 1 H) 5.08 (s, 1 H) 6.04 (d, J=4.55 Hz, 2 H) 6.86 (s, 1 H) 6.89 (s, 1 H) 6.96 (s, 2 H).

Workup

  1. customthe reaction was quenched
  2. additionby adding saturated aqueous ammonium chloride solution (20 mL)
  3. extractionThe mixture was extracted with diethyl ether (2×50 mL)
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was re-crystallized from diethyl ether

Sources & evidence

ORD record
ord-d2c3d64d65f74a628f06fac410ede1a8
Source dataset
uspto-grants-2012_09
Patent number
US08258149B2

Reaction notes

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