Chloride → 8,8-diethyl 9,10-dimethoxy-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline

HRID 2381220Notes

Reaction equation

HRID 2381220 reaction equation
Cl[CH:2]1[NH+:11]2[CH2:12][CH2:13][C:14]3[C:19]([C:10]2=[CH:9][C:8]2[CH:7]=[CH:6][C:5]([O:23][CH3:24])=[C:4]([O:25][CH3:26])[C:3]1=2)=[CH:18][C:17]1[O:20][CH2:21][O:22][C:16]=1[CH:15]=3.[Cl-].[CH2:28]([Mg]Br)[CH3:29].O1CC[CH2:34][CH2:33]1>C(OCC)C>[CH2:33]([C:2]1([CH2:28][CH3:29])[N:11]2[CH2:12][CH2:13][C:14]3[C:19]([C:10]2=[CH:9][C:8]2[CH:7]=[CH:6][C:5]([O:23][CH3:24])=[C:4]([O:25][CH3:26])[C:3]1=2)=[CH:18][C:17]1[O:20][CH2:21][O:22][C:16]=1[CH:15]=3)[CH3:34]

Participants

6

Reactant 4

HCID 312ChlorideHCID 8028TetrahydrofuranHCID 86647495HCID 86647495, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 3280448,8-diethyl 9,10-dimethoxy-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolineYield 67%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 8-chloro-9,10-dimethoxy-5,6-dihydro-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ylium; chloride (0.5 g, 1.2 mmol) in anhydrous diethyl ether (50 mL) at 0° C. was added a solution of ethylmagnesium bromide in tetrahydrofuran (3 M, 4.4 mL, 13 mmol) dropwise. After stirring at 0° C. for 30 min, the reaction was quenched by adding saturated aqueous ammonium chloride solution (30 mL). The mixture was extracted with diethyl ether (2×100 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was re-crystallized from diethyl ether to afford 8,8-diethyl 9,10-dimethoxy-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline (320 mg, 67%). LC/MS m/e calcd for C24H27NO4 (M+H)+: 394.49, observed: 394.1; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.79 (t, J=6.32 Hz, 6 H) 1.78-1.95 (m, 2 H) 2.02-2.18 (m, 2 H) 2.73 (s, 2 H) 3.19 (s, 2 H) 3.74 (d, J=12.88 Hz, 6 H) 5.34 (s, 1 H) 5.99 (s, 2 H) 6.52 (d, J=8.34 Hz, 1 H) 6.74 (s, 1 H) 6.79 (d, J=8.08 Hz, 1 H) 7.18 (s, 1 H).

Workup

  1. customthe reaction was quenched
  2. additionby adding saturated aqueous ammonium chloride solution (30 mL)
  3. extractionThe mixture was extracted with diethyl ether (2×100 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-f0ffe044e6a04280b54456360ac0787e
Source dataset
uspto-grants-2012_09
Patent number
US08258149B2

Reaction notes

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