Oxalyl chloride → 1'-[4(3-methyl-1,2,4-oxadiazol-5-yl)benzyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

HRID 1965807Notes

Reaction equation

HRID 1965807 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:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=1.C(Cl)(=O)C(Cl)=O.O[NH:40][C:41](=[NH:43])[CH3:42]>ClCCl.CN(C)C=O>[CH3:42][C:41]1[N:43]=[C:28]([C:27]2[CH:31]=[CH:32][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)[O:29][N:40]=1

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 461947074-[(2'-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-1'(2'H)-yl)methyl]benzoic acidHCID 178465666HCID 178465666, compound

Product 1

HCID 593525551'-[4(3-methyl-1,2,4-oxadiazol-5-yl)benzyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-oneYield 63%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

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]benzoic acid (0.75 g, 1.7 mmol) in dichloromethane (10 mL) was added oxalyl chloride (0.50 mL, 5.77 mmol) and N,N-dimethylformamide (2 drops, catalytic amount). The mixture was stirred for 16 h at ambient temperature and concentrated in vacuo. The residue was dissolved in pyridine (1 mL) and transferred into a 10 mL microwave reaction vessel with pyridine rinses (2×1 mL). To this solution was added N-hydroxyacetamidine (0.25 g, 3.4 mmol) and the reaction mixture was irradiated at 170° C. for 30 min in a microwave reactor. The reaction mixture was allowed to cool to ambient temperature, concentrated in vacuo and the residue was purified by column chromatography and eluted with a 15% to 50% gradient of ethyl acetate in hexanes, followed by recrystallization from dichloromethane/diethyl ether to afford 1′-[4-(3-methyl-1,2,4-oxadiazol-5-yl)benzyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.50 g, 63%) as a colorless solid: mp 177-178° C. (dichloromethane); 1H NMR (300 MHz, CDCl3) δ 8.08 (d, J=8.1 Hz, 2H), 7.46 (d, J=8.1 Hz, 2H), 7.26-7.13 (m, 2H), 7.06-6.98 (m, 1H), 6.74 (d, J=7.6 Hz, 1H), 6.49 (s, 1H), 6.21 (s, 1H), 5.14 (d, J=16.0 Hz, 1H), 4.94 (d, J=9.0 Hz, 1H), 4.87 (d, J=16.0 Hz, 1H), 4.66 (d, J=8.9 Hz, 1H), 4.21-4.07 (m, 4H), 2.44 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 177.6, 174.9, 167.8, 155.3, 144.7, 141.7, 138.4, 132.2, 128.9, 128.6, 128.0, 124.1, 123.8, 123.8, 120.8, 111.5, 109.1, 99.5, 80.1, 64.5, 63.9, 58.1, 43.9, 11.7; MS (ES+) m/z 467.9 (M+1).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in pyridine (1 mL)
  3. customtransferred into a 10 mL microwave reaction vessel with pyridine rinses (2×1 mL)
  4. customthe reaction mixture was irradiated at 170° C. for 30 min in a microwave reactor
  5. temperatureto cool to ambient temperature
  6. concentrationconcentrated in vacuo
  7. customthe residue was purified by column chromatography
  8. washeluted with a 15% to 50% gradient of ethyl acetate in hexanes
  9. customfollowed by recrystallization from dichloromethane/diethyl ether

Sources & evidence

ORD record
ord-cbc409bd3bb04d9481b81eac85c7522b
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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