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

HRID 2381192Notes

Reaction equation

HRID 2381192 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-].[CH:27]([Mg]Br)=[CH2:28]>C(OCC)C>[CH3:25][O:24][C:4]1[C:5]2[CH:6]([CH:27]=[CH2:28])[N:7]3[CH2:20][CH2:19][C:18]4[C:13]([C:8]3=[CH:9][C:10]=2[CH:11]=[CH:12][C:3]=1[O:2][CH3:1])=[CH:14][C:15]1[O:23][CH2:22][O:21][C:16]=1[CH:17]=4

Participants

4

Reactant 2

HCID 12456Berberine hydrochlorideHCID 178418507HCID 178418507, compound

Product 1

HCID 498059699,10-dimethoxy-8-vinyl-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolineYield 101.6%

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 vinylmagnesium bromide solution (1.0 M in tetrahydrofuran, 13 mL, 13 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 9,10-dimethoxy-8-vinyl-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline (480 mg, 98%). LC/MS m/e calcd for C22H21NO4 (M+H)+: 364.32, observed: 364.1; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.74-2.84 (m, 2 H) 3.16-3.24 (m, 2 H) 3.75 (s, 3 H) 3.77 (s, 3 H) 4.97 (d, J=10.11 Hz, 1 H) 5.06 (dd, J=4.55, 2.53 Hz, 2 H) 5.85-5.93 (m, 1 H) 5.95 (s, 1 H) 6.00 (d, J=5.31 Hz, 2 H) 6.72 (d, J=8.34 Hz, 1 H) 6.77 (s, 1 H) 6.86 (d, J=8.34 Hz, 1 H) 7.25 (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-7a6416ed40d64f159bcc89daeb3c76e8
Source dataset
uspto-grants-2012_09
Patent number
US08258149B2

Reaction notes

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