Dimethylformamide dimethyl acetal → 7-bromo-5-nitro-1H-isochromen-1-one

HRID 577596Notes

Reaction equation

HRID 577596 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N+:13]([O-:15])=[O:14])[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].COC(OC)N(C)C>CN(C)C=O>[Br:1][C:2]1[CH:11]=[C:6]2[C:5]([CH:12]=[CH:10][O:9][C:7]2=[O:8])=[C:4]([N+:13]([O-:15])=[O:14])[CH:3]=1

Participants

4

Reactant 2

HCID 78373Dimethylformamide dimethyl acetalHCID 24727998Methyl 5-bromo-2-methyl-3-nitrobenzoate

Product 1

HCID 867238247-bromo-5-nitro-1H-isochromen-1-oneYield 33.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of methyl 5-bromo-2-methyl-3-nitrobenzoate (29.0 g, 106 mmol) and N,N-dimethylformamide dimethyl acetal (42.0 mL, 317 mmol) in N,N-dimethylformamide (200 mL) was stirred at 110° C. overnight. After cooling to room temperature, the reaction mixture was partitioned between ethyl acetate (300 mL) and water (300 mL). The organic phase was separated, washed with water (2×300 mL) and brine (1×3 00 mL), concentrated to dryness in the presence of silica gel, and purified by silica gel chromatography (eluting with a gradient of 0-80% ethyl acetate in heptane) to give 7-bromo-5-nitro-1H-isochromen-1-one (293a, 9.62 g, 32% yield) as a solid. 1H NMR (400 MHz, CDCl3-d) δ 8.76 (d, J=1.47 Hz, 1H), 8.60 (d, J=2.20 Hz, 1H), 7.46 (d, J=6.11 Hz, 1H), 7.34 (d, J=6.11 Hz, 1H). MS: 269 [M+1]

Workup

  1. customthe reaction mixture was partitioned between ethyl acetate (300 mL) and water (300 mL)
  2. customThe organic phase was separated
  3. washwashed with water (2×300 mL) and brine (1×3 00 mL)
  4. concentrationconcentrated to dryness in the presence of silica gel
  5. custompurified by silica gel chromatography (
  6. washeluting with a gradient of 0-80% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-9ee8dce8380047d98ce914a95e790d09
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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