(Z)-ethyl 2-(4-bromo-2-nitrobenzoyl)-3-(dimethylamino)acrylate → ethyl 5-(4-bromo-2-nitrophenyl)-1-(1,4-dioxepan-6-yl)-1H-pyrazole-4-carboxylate

HRID 1043873Notes

Reaction equation

HRID 1043873 reaction equation
[Br:1][C:2]1[CH:19]=[CH:18][C:5]([C:6](/[C:8](=[CH:14]/[N:15](C)C)/[C:9]([O:11][CH2:12][CH3:13])=[O:10])=O)=[C:4]([N+:20]([O-:22])=[O:21])[CH:3]=1.Cl.[O:24]1[CH2:30][CH:29]([NH:31]N)[CH2:28][O:27][CH2:26][CH2:25]1>C(#N)C.O>[Br:1][C:2]1[CH:19]=[CH:18][C:5]([C:6]2[N:31]([CH:29]3[CH2:28][O:27][CH2:26][CH2:25][O:24][CH2:30]3)[N:15]=[CH:14][C:8]=2[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:4]([N+:20]([O-:22])=[O:21])[CH:3]=1

Participants

5

Reactant 2

HCID 86686314(Z)-ethyl 2-(4-bromo-2-nitrobenzoyl)-3-(dimethylamino)acrylateHCID 86686315(1,4-Dioxepan-6-yl)hydrazine hydrochloride

Product 1

HCID 86686313ethyl 5-(4-bromo-2-nitrophenyl)-1-(1,4-dioxepan-6-yl)-1H-pyrazole-4-carboxylateYield 53.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of (Z)-ethyl 2-(4-bromo-2-nitrobenzoyl)-3-(dimethylamino)acrylate (642 mg) in acetonitrile (8 mL) was added a solution of (1,4-dioxepan-6-yl)hydrazine hydrochloride (341 mg) obtained in Preparation Example 16 in water (2 mL) at room temperature. The reaction mixture was stirred at room temperature overnight and further stirred at 50° C. for 9.5 hours. The reaction mixture was returned to room temperature and partitioned by adding ethyl acetate and water. The aqueous layer was extracted again with ethyl acetate. The combined organic layers were sequentially washed with the saturated aqueous sodium bicarbonate solution and brine, and dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/heptane, 20 to 33%) to give the title compound (408 mg).

Workup

  1. stirringfurther stirred at 50° C. for 9.5 hours
  2. customwas returned to room temperature
  3. custompartitioned
  4. additionby adding ethyl acetate and water
  5. extractionThe aqueous layer was extracted again with ethyl acetate
  6. washThe combined organic layers were sequentially washed with the saturated aqueous sodium bicarbonate solution and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate/heptane, 20 to 33%)

Sources & evidence

ORD record
ord-9d0584300e4b45c2a69e2fd7d57e561d
Source dataset
uspto-grants-2013_10
Patent number
US08563565B2

Reaction notes

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