Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
  • C07C227/04—Formation of amino groups in compounds containing carboxyl groups
  • C07C227/10—Formation of amino groups in compounds containing carboxyl groups with simultaneously increasing the number of carbon atoms in the carbon skeleton

Definitions

• the present invention relates to a novel process for the preparation of substituted propenoic acid esters using active methylene compounds and N, N dimethyl formamide-dimethyl sulfate complex.
• Substituted propenoic acid esters especially amino-substituted derivatives like ⁇ -amino acrylic acid esters are significantly important in the synthesis of quinolones (JP 02215749 A2, 1990; Leibigs Ann. Chem. 29-37, 1987).
• Nalidixic acid was the first quinolone introduced to clinical practice, and is still in use for treatment of urinary tract infections caused by gram- negative pathogens.
• the present invention discloses a safe, economical and facile route for the preparation of substituted propenoic acid esters.
• U S Patent No.4,772,711 discloses a method for the preparation of 3 anrino acrylic acid esters by reacting an alkali salt of a beta hydroxy acrylic acid ester with an amine salt.
• U S Patent No.5,030,747 discloses a method of preparation of beta amino acrylic acid esters by reaction of beta hydroxy acrylic acid ester alkali metal salts with ammomum salts in an aprotic organic solvent, or in an aprotic organic solvent in admixture with a protic organic solvent miscible with the aprotic solvent, to give high 90% yield of the reaction product compared to 75% yield of the Englaender method (U S Patent No.4, 772,711).
• the starting alkali salt of beta hydroxy acrylic acid ester for both the above methods of US Patent Nos.4,772,71 1 and 5,030,747 is obtained from carbon monoxide, alcoholate and acetic acid esters in a pressure reaction requiring 20 to 50 bar.
• both these methods requires high pressure apparatus.
• the high toxicity and flammability of carbon monoxide demands special safety devices.
• US Patent No.5,446, 192 discloses a method for production of ⁇ -amino acrylic acid esters by reacting acetic acid esters with
• amino acid esters at 0.5 to 10 bar (preferably 1 to 5 bar) and 50-70°C (preferably 80°C to 150°C) in an aprotic polar solvent. Apart from the high temperature and pressure required by the process, the amino acid esters are costly.
• the object of the invention is to provide for a safe, economical, facile route for the preparation of substituted propenoic acid esters.
• the present invention provides a process for the preparation of substituted propenoic acid esters of general formula I.
• R is C 1 -C 4 alkyl group
• said process comprises,
• Ri is Na + or K + and R 2 is C 1 -C 4 alkyl group, with,
• the present invention relates to a cost effective and safe process.
• the present invention provides a process for the preparation of substituted propenoic acid esters of formula (I) :
• R ⁇ is Na + or K + and R 2 is C r C 4 alkyl group, with, N, N-
• the R 2 group of the active methylene compound of general formula (II) used in the present invention is preferably methyl or ethyl.
• the active methylene compound is preferably cooled before the reaction, to a temperature range of 5-20°C and preferably to around 10°C.
• the reaction between compounds II and III is carried out in an inert atmosphere, preferably nitrogen atmosphere.
• N, N-dimethylfo ⁇ namide-dimethylsulfate complex i.e.
• N, N-d memylamino methoxymethylium methyl sulfate (III) was prepared according to literature procedure (Organic Synthesis, Collective Vol.V).
• reaction according to the process of the invention may be represented by the following scheme :
• Ethylene dichloride is preferably used as solvent, but benzene, toluene or chloroform can also be used.
• methyl alkali malonate such as methyl potassium malonate (II) was treated with N, N-dimethylamino methoxymethylium methyl sulfate (III) to give 2-propenoic acid, 3- (dimethylamino), methyl ester, (E) in 68% yield.
• EXAMPLE 1 Preparation of methyl potassium malonate by using dimethyl malonate.
• a 1 lit. round bottom flask was charged with 150ml. of methanol under nitrogen. To it was added 100 gm. of diethyl malonate and it was cooled to 0- 15°C, preferably to 10°C. To this cooled solution, methanolic potassium hydroxide solution (prepared by the slow addition of 40 gm. of potassium hydroxide in 150 ml. of methanol under nitrogen) was added. The reaction mixture was stirred for 7 hr. The reaction mixture was then cooled to 5°C for 30 min. The solid which separated out was filtered to give 85 gm. of methyl malonate.
• methyl sodium malonate was also prepared, using the above procedures.
• EXAMPLE 4 Preparation of ethyl potassium malonate by using diethyl malonate.
• a 250 ml. round bottom flask was charged with 40 ml. of ethanol under nitrogen. To it was added 20 gm. of diethylmalonate and it was cooled to 5- 20°C, preferably to 10°C. To this cooled solution, ethanolic potassium hydroxide solution (prepared by slow addition of 8 gm. of potassium hydroxide in 30 ml of ethanol under nitrogen) was added. The reaction mixture was stirred for 7 hr. The reaction mixture was then cooled to 0-10°C,
• EXAMPLE 5 Preparation of ethyl potassium malonate by using dimethyl malonate.
• a 250 ml. round bottom flask was charged with 40 ml. of ethanol under nitrogen. To it was added 20 gm. of dimethylmalonate and it was cooled to 0- 15°C, preferably to 10°C. To this cooled solution, ethanolic potassium hydroxide solution (prepared by slow addition of 9.9 gm. of potassium hydroxide in 30 ml. of ethanol under nitrogen) was added. The reaction mixture was stirred for 7 hr. The reaction mixture was then cooled to 5°C for 30 min. The solid which separated out was filtered to give 15 gm. of ethyl potassium malonate.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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• 1999
  • 1999-02-22 EP EP99902780A patent/EP1091927A1/de not_active Withdrawn
  • 1999-02-22 JP JP2000557221A patent/JP2002519337A/ja active Pending
  • 1999-02-22 WO PCT/IB1999/000321 patent/WO2000000460A1/en not_active Application Discontinuation
  • 1999-02-22 AU AU22959/99A patent/AU2295999A/en not_active Abandoned

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