Hydroxylamine → HCID 86761613, compound

HRID 2385542Notes

Reaction equation

HRID 2385542 reaction equation
[CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11]#[N:12])[C:5]=2[C:4]2([C:24]3[C:15](=[CH:16][C:17]4[O:22][CH2:21][CH2:20][O:19][C:18]=4[CH:23]=3)[O:14][CH2:13]2)[C:3]1=O.[NH2:26][OH:27].[OH2:28]>CS(C)=O>[OH:27][N:26]=[C:11]([C:6]1[C:5]2[C:4]3([C:24]4=[CH:23][C:18]5[O:19][CH2:20][CH2:21][O:22][C:17]=5[CH:16]=[C:15]4[O:14][CH2:13]3)[C:3](=[O:28])[N:2]([CH3:1])[C:10]=2[CH:9]=[CH:8][CH:7]=1)[NH2:12]

Participants

5

Reactant 3

HCID 787HydroxylamineHCID 962WaterHCID 59352298HCID 59352298, compound

Product 1

HCID 86761613HCID 86761613, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 1′-methyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carbonitrile (0.35 g, 1.05 mmol) in dimethylsulfoxide (10 mL) was added hydroxylamine (50% w/w solution in water, 3.0 mL). The reaction mixture was stirred for 16 h at ambient temperature, poured into water (50 mL) and extracted with ethyl acetate (3×100 mL). The combined organic extracts were washed with brine (2×50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was triturated in hexanes to afford N′-hydroxy-1′-methyl-2′-oxo-3,7-dihydro-2H-spiro[benzofuro[5,6-b][1,4]dioxine-8,3′-indoline]-4′-carboximidamide (0.37 g) as a colorless solid. To a 10 mL microwave reaction vessel were added N′-hydroxy-1′-methyl-2′-oxo-3,7-dihydro-2H-spiro[benzofuro[5,6-b][1,4]dioxine-8,3′-indoline]-4′-carboximidamide (0.20 g, 0.54 mmol), acetic anhydride (0.50 mL) and pyridine (2.00 mL). The solution was heated at 160° C. for 0.5 h in a microwave reactor, allowed to cool to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography and eluted with hexanes/ethyl acetate (3/1) followed by recrystallization from diethyl ether to afford 1-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.08 g, 37%) as a colorless solid: mp 199-201° C. (diethyl ether); 1H NMR (300 MHz, CDCl3) δ 7.70 (dd, J=8.0, 0.8 Hz, 1H), 7.46 (t, J=7.9 Hz, 1H), 7.03 (dd, J=7.8, 0.8 Hz, 1H), 6.39 (s, 1H), 6.03 (s, 1H), 5.14 (d, J=8.6 Hz, 1H), 4.82 (d, J=8.6 Hz, 1H), 4.16-4.00 (m, 4H), 3.28 (s, 3H), 2.50 (s, 3H); MS (ES+) m/z 391.9 (M+1).

Workup

  1. extractionextracted with ethyl acetate (3×100 mL)
  2. washThe combined organic extracts were washed with brine (2×50 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated in hexanes

Sources & evidence

ORD record
ord-fe541940994c49b78d76b799253e6ed4
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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