2,6-Dichloroaniline → Methyl 3,5-dibromo-4-{(1Z)-3-[(2,6-dichlorophenyl)amino]-3-oxoprop-1-enyl}benzoate

HRID 394208

Reaction equation

HRID 394208 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[C:4]([Br:12])[C:3]=1/[CH:13]=[CH:14]\[C:15]([OH:17])=O.C(Br)(=O)C(Br)=O.C(N(C(C)C)CC)(C)C.[Cl:33][C:34]1[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[C:35]=1[NH2:36]>ClCCl.[Cl-].[Na+].O.CN(C)C=O>[Br:12][C:4]1[CH:5]=[C:6]([CH:7]=[C:2]([Br:1])[C:3]=1/[CH:13]=[CH:14]\[C:15]([NH:36][C:35]1[C:34]([Cl:33])=[CH:40][CH:39]=[CH:38][C:37]=1[Cl:41])=[O:17])[C:8]([O:10][CH3:11])=[O:9]

Participants

8

Reactant 4

HCID 118462,6-DichloroanilineHCID 81531DiisopropylethylamineHCID 84841Ethanedioyl dibromideHCID 69848595(2Z)-3-[2,6-Dibromo-4-(methoxycarbonyl)phenyl]prop-2-enoic acid

Product 1

HCID 69919937Methyl 3,5-dibromo-4-{(1Z)-3-[(2,6-dichlorophenyl)amino]-3-oxoprop-1-enyl}benzoate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of (2Z)-3-[2,6-dibromo-4-(methoxycarbonyl)phenyl]prop-2-enoic acid (1.24 g) (contaminated with 20% of the E isomer) in dichloromethane (34 mL) at 0° C. under nitrogen atmosphere was added oxalyl bromide (2 mL of a 2M solution in dichloromethane) followed by dimethylformamide (170 μL). The mixture was then warmed to rt and stirred until all gas evolution had ceased. The reaction was cooled again to 0° C. where diisopropylethylamine (83 μL) and 2,6-dichloroaniline (607 mg) were added and the reaction warmed to rt and stirred for 16 h. The reaction mixture was then poured into brine and extracted into ethyl acetate. A small amount of unreacted starting acid was removed by washing the organic layer with saturated sodium bicarbonate solution, before drying over MgSO4 and concentrating. The residue was purified by column chromatography on silica gel to give the title compound still contaminated with 20% of the E isomer. 1H NMR (500 MHz, CDCl3): δ 8.99 (br.s, 1H, Z isomer); 8.26 (br.s, 1H, E isomer); 8.20 (s, 1H, Z isomer); 7.80-6.40 (m, 6H); 3.96 (s, 3H, E isomer); 3.92 (s, 3H, Z isomer). Mass spectrum: m/z 507 (M+H).

Workup

  1. customat 0° C.
  2. additionwere added
  3. temperaturethe reaction warmed to rt
  4. stirringstirred for 16 h
  5. extractionextracted into ethyl acetate
  6. customwas removed
  7. washby washing the organic layer with saturated sodium bicarbonate solution
  8. dry with materialbefore drying over MgSO4
  9. concentrationconcentrating
  10. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-6e841387e3284230988fd58affca5cc9
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Linked notes

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