Water → 2-[(2'-Oxo-2,2',3,3'-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,1'-inden]-3'-yl)methyl]pyridine-3-carbonitrile

HRID 1407837Notes

Reaction equation

HRID 1407837 reaction equation
Br[C:2]1[C:3]([CH2:8][CH:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]3([C:29]4[C:20](=[CH:21][C:22]5[O:27][CH2:26][CH2:25][O:24][C:23]=5[CH:28]=4)[O:19][CH2:18]3)[C:10]2=[O:30])=[N:4][CH:5]=[CH:6][CH:7]=1.[C-:31]#[N:32].[Na+].O>CN1CCCC1=O.O.O.O.O.O.O.[Ni](Cl)Cl>[O:30]=[C:10]1[CH:9]([CH2:8][C:3]2[C:2]([C:31]#[N:32])=[CH:7][CH:6]=[CH:5][N:4]=2)[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]21[C:29]1[C:20](=[CH:21][C:22]3[O:27][CH2:26][CH2:25][O:24][C:23]=3[CH:28]=1)[O:19][CH2:18]2

Participants

6

Reactant 3

HCID 962WaterHCID 8929Sodium CyanideHCID 673576033'-[(3-Bromopyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]-benzodioxine-8,1'-inden]-2'(3'H)-one

Product 1

HCID 673567312-[(2'-Oxo-2,2',3,3'-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,1'-inden]-3'-yl)methyl]pyridine-3-carbonitrileYield 289%

Reagents, catalysts & solvents 2

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
200 °C

Procedure

3′-[(3-Bromopyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,1′-inden]-2′(3′H)-one (0.233 g, 0.500 mmol), nickel (II) chloride hexahydrate (0.113 g, 0.500 mmol), and sodium cyanide (0.050 g, 1.0 mmol) were combined in 1-methyl-2-pyrrolidone (1 mL) and heated at 200° C. for 30 min under microwave irradiation. The reaction mixture was allowed to cool to ambient temperature, poured into water (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine (3×20 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was subjected to column chromatography, and eluted with a 50% to 75% gradient of ethyl acetate in hexanes, to afford 2-[(2′-oxo-2,2′,3,3′-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,1′-inden]-3′-yl)methyl]pyridine-3-carbonitrile (0.593 g, 29%) as a colorless solid: mp 230-233° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.71 (dd, J=4.8, 1.4 Hz, 1H), 8.38 (dd, J=7.9, 1.5 Hz, 1H), 7.56 (dd, J=7.8, 4.9 Hz, 1H), 7.27-7.15 (m, 2H), 7.04 (d, J=7.5 Hz, 1H), 6.98 (d, J=7.9 Hz, 1H), 6.50 (s, 1H), 6.38 (s, 1H), 5.30 (s, 2H), 4.74 (ABq, 2H), 4.19-4.11 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 177.3, 158.2, 155.0, 153.1, 144.6, 143.1, 142.1, 138.2, 132.4, 129.1, 124.0, 123.4, 121.9, 116.5, 112.2, 109.8, 108.0, 99.1, 79.8, 64.7, 64.1, 57.7, 44.1; MS (ES+) m/z 412.0 (M+1).

Workup

  1. temperatureto cool to ambient temperature
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. washThe combined organic layers were washed with brine (3×20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washeluted with a 50% to 75% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-016e0847816e4d6480cb8bdb5585068a
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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