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

HRID 2381195Notes

Reaction equation

HRID 2381195 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][N+:7]3[CH2:20][CH2:19][C:18]4[C:13](=[CH:14][C:15]5[O:23][CH2:22][O:21][C:16]=5[CH:17]=4)[C:8]=3[CH:9]=2)[C:4]=1[O:24][CH3:25].[Cl-].[CH2:27]([Mg]Cl)[CH:28]=[CH2:29]>C(OCC)C>[CH2:29]([CH:6]1[N:7]2[CH2:20][CH2:19][C:18]3[C:13]([C:8]2=[CH:9][C:10]2[CH:11]=[CH:12][C:3]([O:2][CH3:1])=[C:4]([O:24][CH3:25])[C:5]1=2)=[CH:14][C:15]1[O:23][CH2:22][O:21][C:16]=1[CH:17]=3)[CH:28]=[CH2:27]

Participants

4

Reactant 2

HCID 12456Berberine hydrochlorideHCID 178418473HCID 178418473, compound

Product 1

HCID 111531248-allyl-9,10-dimethoxy-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolineYield 51%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of berberine hydrochloride (500 mg, 1.3 mmol) in anhydrous diethyl ether (50 mL) at 0° C. was added allylmagnesium chloride solution (1.7 M in tetrahydrofuran, 8 mL, 13 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 8-allyl-9,10-dimethoxy-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline (250 mg, 49%). LC/MS m/e calcd for C23H23NO4 (M+H)+: 378.44, observed: 378.2; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.34 (t, J=6.32 Hz, 2 H) 2.66-2.75 (m, 1 H) 2.79-2.87 (m, 1 H) 3.26-3.32 (m, 1 H) 3.35-3.44 (m, 1 H) 3.78 (d, J=6.32 Hz, 6 H) 4.78-4.85 (m, 2 H) 4.86 (s, 1 H) 5.68-5.80 (m, 1 H) 5.87 (s, 1 H) 6.00 (d, J=3.54 Hz, 2 H) 6.68 (d, J=8.34 Hz, 1 H) 6.77 (s, 1 H) 6.84 (d, J=8.59 Hz, 1 H) 7.23 (s, 1 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-ca28f448a12742f4a2a0a4ab69ab8e01
Source dataset
uspto-grants-2012_09
Patent number
US08258149B2

Reaction notes

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