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

HRID 2381190Notes

Reaction equation

HRID 2381190 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]1([Mg]Cl)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(OCC)C>[CH3:25][O:24][C:4]1[C:5]2[CH:6]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[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 178478979HCID 178478979, compound

Product 1

HCID 33628779,10-dimethoxy-8-phenyl-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolineYield 67.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of berberine hydrochloride (400 mg, 1.08 mmol) in anhydrous diethyl ether (50 mL) at 0° C. was added phenylmagnesium chloride solution (2.8 mL, 2.7 mmol) dropwise. After stirring at 0° C. for 10 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 9,10-dimethoxy-8-phenyl-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline (300 mg, 67%). LC/MS m/e calcd for C26H23NO4 (M+H)+: 414.48, observed: 414.2; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.67-2.90 (m, 3 H) 3.35-3.41 (m, 1 H) 3.49 (s, 3 H) 3.74 (s, 3 H) 5.70 (s, 1 H) 5.99 (d, J=1.52 Hz, 2 H) 5.98 (s, 1 H) 6.72 (s, 1 H) 6.80 (m, 1 H) 6.88 (m, 1 H) 7.16-7.28 (m, 4 H) 7.35 (d, J=7.07 Hz, 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-90430f849a7e466d81c0abdc1f986410
Source dataset
uspto-grants-2012_09
Patent number
US08258149B2

Reaction notes

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