Tetrahydrofuran → 2,3-Dimethoxy-7-[2-(3-pyridyloxy)ethyl]-4,5,6,7,8,9-hexahydro-1H-benzo[a]cycloheptene-1,4-dione

HRID 2268549Notes

Reaction equation

HRID 2268549 reaction equation
C[O:2][C:3]1[C:8]2[CH2:9][CH2:10][CH:11]([CH2:14][CH2:15][O:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)[CH2:12][CH2:13][C:7]=2[C:6]([O:23]C)=[C:5]([O:25][CH3:26])[C:4]=1[O:27][CH3:28].N1C(C(O)=O)=CC=CC=1C(O)=O.C1COCC1.O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+]>C(=O)(O)[O-].[Na+].O>[CH3:28][O:27][C:4]1[C:3](=[O:2])[C:8]2[CH2:9][CH2:10][CH:11]([CH2:14][CH2:15][O:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)[CH2:12][CH2:13][C:7]=2[C:6](=[O:23])[C:5]=1[O:25][CH3:26]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 103672,6-Pyridinedicarboxylic acidHCID 180504Ceric ammonium nitrateHCID 183486323-[2-(1,2,3,4-Tetramethoxy-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-7-yl)ethoxy]pyridine

Product 1

HCID 183486652,3-Dimethoxy-7-[2-(3-pyridyloxy)ethyl]-4,5,6,7,8,9-hexahydro-1H-benzo[a]cycloheptene-1,4-dioneYield 71.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a mixture of 3-[2-(1,2,3,4-tetramethoxy-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-7-yl)ethoxy]pyridine (470 mg), pyridine-2,6-dicarboxylic acid (607 g), THF (10 ml), and water (5 ml) was added an water (5 ml) solution of CAN (2.65 g) with cooling with ice. After being stirred for 15 min, the reaction mixture was diluted with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, water, and saturated aqueous sodium chloride and dried. The solvent was removed in vacuo. The residue was purified by alumina column chromatography (ethyl acetate) and then with recrystallization from hexane-ethyl acetate to obtain the entitled compound (310 mg).

Workup

  1. temperaturewith cooling with ice
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate, water, and saturated aqueous sodium chloride
  4. customdried
  5. customThe solvent was removed in vacuo
  6. customThe residue was purified by alumina column chromatography (ethyl acetate)
  7. customwith recrystallization from hexane-ethyl acetate

Sources & evidence

ORD record
ord-bd554b6115004a5dbf3abc6a28cee182
Source dataset
uspto-grants-2001_12
Patent number
US06326369B1

Reaction notes

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