Hydroxylamine → HCID 59352196, compound

HRID 1965706Notes

Reaction equation

HRID 1965706 reaction equation
[O:1]=[C:2]1[C:10]2([C:22]3[C:13](=[CH:14][C:15]4[O:20][CH2:19][CH2:18][O:17][C:16]=4[CH:21]=3)[O:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=1.[NH2:32][OH:33].N1[CH:39]=[CH:38]C=CC=1.C(OC(=O)C)(=O)C>CS(C)=O.O>[CH3:38][C:39]1[O:33][N:32]=[C:28]([C:27]2[CH:30]=[CH:31][C:24]([CH2:23][N:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[C:10]4([C:22]5[C:13](=[CH:14][C:15]6[O:20][CH2:19][CH2:18][O:17][C:16]=6[CH:21]=5)[O:12][CH2:11]4)[C:2]3=[O:1])=[CH:25][CH:26]=2)[N:29]=1

Participants

7

Reactant 4

HCID 787HydroxylamineHCID 1049PyridineHCID 7918Acetic AnhydrideHCID 46194709HCID 46194709, compound

Product 1

HCID 59352196HCID 59352196, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-[(2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)methyl]benzonitrile (0.41 g, 1.0 mmol) in dimethylsulfoxide (20 mL) was added hydroxylamine (50% w/w solution in water, 2.0 mL, 33 mmol). The mixture was heated at 80° C. for 16 h, allowed to cool to ambient temperature and diluted with water (50 mL), causing a precipitate to be deposited. The solid was collected by filtration and combined with pyridine (2.0 mL) and acetic anhydride (0.2 g, 2.0 mmol) in a 10 mL microwave reaction vessel. The mixture was heated at 170° C. for 15 min under microwave irradiation, allowed to cool to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography and eluted with a 15% to 50% gradient of ethyl acetate in hexanes to afford 1′-[4-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.52 g, 85%) as a colorless solid: mp 174-175° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, DMSO-d6) δ 8.06-8.00 (m, 2H), 7.42 (d, J=8.3 Hz, 2H), 7.22-7.13 (m, 2H), 7.04-6.97 (m, 1H), 6.75 (d, J=7.7 Hz, 1H), 6.50 (s, 1H), 6.23 (s, 1H), 5.12 (d, J=15.8 Hz, 1H), 4.94 (d, J=8.9 Hz, 1H), 4.85 (d, J=15.8 Hz, 1H), 4.66 (d, J=8.9 Hz, 1H), 4.21-4.07 (m, 4H), 2.63 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 177.6, 176.6, 168.0, 155.3, 144.7, 141.9, 138.4, 132.2, 128.9, 128.0, 127.8, 126.5, 124.0, 123.6, 120.9, 111.5, 109.2, 99.5, 80.1, 58.1, 43.9, 12.4; MS (ES+) m/z 467.9 (M+1).

Workup

  1. temperatureto cool to ambient temperature
  2. filtrationThe solid was collected by filtration
  3. temperatureThe mixture was heated at 170° C. for 15 min under microwave irradiation
  4. temperatureto cool to ambient temperature
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography
  7. washeluted with a 15% to 50% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-0ada0023183e4beeb3ff96d3505f9102
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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