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

HRID 2381193Notes

Reaction equation

HRID 2381193 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-].[C:27]([Mg]Br)([CH3:29])=[CH2:28]>C(OCC)C>[C:27]([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)([CH3:29])=[CH2:28]

Participants

4

Reactant 2

HCID 12456Berberine hydrochlorideHCID 178456138HCID 178456138, compound

Product 1

HCID 469442628-isopropenyl-9,10-dimethoxy-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolineYield 101.9%

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 (100 mL) at 0° C. was added isopropenylmagnesium bromide solution (0.5 M in tetrahydrofuran, 52 mL, 26 mmol) dropwise. After stirring at 0° C. for 2 h, 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-isopropenyl-9,10-dimethoxy-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline (500 mg, 98%). LC/MS m/e calcd for C23H23NO4 (M+H)+: 378.44, observed: 378.0; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.57 (s, 3 H) 2.72-2.83 (m, 2 H) 3.00-3.09 (m, 1 H) 3.12-3.20 (m, 1 H) 3.71 (s, 3 H) 3.77 (s, 3 H) 4.61 (s, 1 H) 4.92 (d, J=1.52 Hz, 1 H) 5.19 (s, 1 H) 5.80 (s, 1 H) 6.00 (d, J=2.27 Hz, 2 H) 6.69 (d, J=8.59 Hz, 1 H) 6.77 (s, 1 H) 6.85 (d, J=8.34 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-05230a499714441e9f724be5264dc9f5
Source dataset
uspto-grants-2012_09
Patent number
US08258149B2

Reaction notes

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