Ethyl 2-methylacetoacetate → HCID 178432198, compound

HRID 1361451Notes

Reaction equation

HRID 1361451 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)[NH2:5].[CH3:17][CH:18]([C:24]([CH3:26])=O)[C:19](OCC)=[O:20].ClC1C(OC2C=CC(Cl)=CC=2)=CC=C2C=1C(O)=C(C)C(C)=N2>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:6]([C:19]([OH:20])=[C:18]([CH3:17])[C:24]([CH3:26])=[N:5]2)=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 701Ethyl 2-methylacetoacetateHCID 906443-Chloro-4-(4-chlorophenoxy)anilineHCID 178432212HCID 178432212, compound

Product 1

HCID 178432198HCID 178432198, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture composed of 2.2 g of 3-chloro-4-(4-chlorophenoxy)-aniline, 2.63 g of ethyl 2-methylacetoacetate, and 0.5 mL of ethanol was added dropwise to 3.8 g of polyphosphoric acid heated to 150° C. The mixed solution was stirred at 150 to 160° C. while removing ethanol by evaporation for 3 hr. The reaction solution was poured into 175 mL of iced water containing 2 mL of concentrated hydrochloric acid to produce crystals. The crystals were collected by filtration and were recrystallized from water/methanol to give 2.8 g of a mixture of 5-chloro-6-(4-chlorophenoxy)-4-hydroxy-2,3-dimethyl-quinoline with 7-chloro-6-(4-chlorophenoxy)-4-hydroxy-2,3-dimethyl-quinoline (yield 93%). The mixture (2.8 g) was stirred in 42 mL of acetic anhydride with heating at 120 to 125° C. for one hr. The reaction solution was concentrated, ethyl acetate was then added to the concentrate, the mixture was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and the solvent was removed under the reduced pressure to give a crude product. The crude product was purified by column chromatography on silica gel (BW300, manufactured by Fuji Sylysia Chemical Ltd., solvent: n-hexane/ethyl acetate) to give 1.03 g of 4-acetoxy-5-chloro-6-(4-chlorophenoxy)-2,3-dimethyl-quinoline (yield 32.6%) and 0.68 g of 4-acetoxy-7-chloro-6-(4-chlorophenoxy)-2,3-dimethyl-quinoline (yield 21.0%).

Workup

  1. customwhile removing ethanol
  2. customby evaporation for 3 hr
  3. additionThe reaction solution was poured into 175 mL of iced water containing 2 mL of concentrated hydrochloric acid
  4. customto produce crystals
  5. filtrationThe crystals were collected by filtration
  6. customwere recrystallized from water/methanol

Sources & evidence

ORD record
ord-3f73b1ee0ae040e8a2d90cf3f6bbdee2
Source dataset
uspto-grants-2011_02
Patent number
US07880006B2

Reaction notes

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