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EP-3812364-B1 - PRODUCTION METHOD FOR ALPHA-FLUOROACRYLIC ACID COMPOUND

EP3812364B1EP 3812364 B1EP3812364 B1EP 3812364B1EP-3812364-B1

Inventors

  • GOTOU, AKIHIRO
  • KISHIKAWA, YOSUKE
  • HOSHIYA, NAOYUKI
  • MATSUURA, MAKOTO

Dates

Publication Date
20260506
Application Date
20190621

Claims (8)

  1. A method for producing a compound of formula (1) or a salt thereof: wherein R 1 , R 2 each independently are H, halogen, alkyl, fluoroalkyl, or optionally substituted aryl; R 3o is H or R 3 ; and R 3 is alkyl, fluoroalkyl or optionally substituted aryl; comprising step A of reacting a compound of formula (2) with carbon monoxide and an alcohol of formula (3): R 3 -OH (3) wherein R 1 -R 3 are as defined above, in the presence of - palladium, - a double bond-containing compound (α) of the formula wherein R b1 is H or C 1-6 -alkyl, R b2 is H or C 1-6 -alkyl, Y b1 is =O or =CH-R yb1 , yb2 is -H, =O or =CH-R yb2 , R yb1 and R yb2 each independently are C 6-14 -aryl, or R yb1 and R yb2 may together form -L y -, wherein L y is linear C 1-2 -alkanediyl optionally having one or more methyl side chains, L b is a bond, C 1-3 -alkanediyl, or -C(=O)-, - a diphosphine compound (β) having, on each phosphorus atom, at least one substituent selected from alkyl and cycloalkyls, and - a base, with the proviso that, in the reaction, the palladium, together with the compound of formula (2), the compound (α), the compound (β), or carbon monoxide, or with one or more of these, may form a palladium complex (A), to obtain the compound represented by formula (1) or a salt thereof; wherein the amount of the palladium complex (A) is ≤ 0.00025 mol per mole of the compound of formula (2).
  2. The method of claim 1, wherein R 1 and R 2 each are H.
  3. The method of claim 1 or 2, wherein R yb1 and R yb2 each independently are C 6-14 -aryl.
  4. The method of any of claims 1-3, wherein Y b1 is =O, Y b2 is =O, and L b is methanediyl optionally having a side chain.
  5. The method of any of claims 1-3, wherein Y b1 is =CH-R yb1 , Y b2 is =CH-R yb2 , and L b is a bond, -C(=O)-, methanediyl, or 1,2-ethanediyl.
  6. The method of any of claims 1-3, wherein R b1 is H, Y b1 is =CH-R yb1 , Y b2 is H, and L b is a bond.
  7. The method of any of claims 1-6, wherein the base is an amine.
  8. The method of any of claims 1-7, wherein step (A) is performed at a temperature of ≥ 20°C.

Description

Technical Field The present invention relates to a method for producing an α-fluoroacrylic acid compound. Background Art α-Fluoroacrylic acid compounds are useful as synthetic intermediates of pharmaceuticals (e.g., antibiotics), synthetic intermediates for sheath materials of optical fibers, synthetic intermediates of coating materials, synthetic intermediates of semiconductor resist materials, and monomers of functional polymers. Of α-fluoroacrylic acid compounds, a conventional method proposed for producing an α-fluoroacrylic acid ester at a high yield is, for example, a method for producing a compound of formula (1): wherein R1 and R2 each independently are alkyl, fluoroalkyl, aryl optionally having one or more substituents, halogen or hydrogen;R3o is hydrogen or R3; andR3 is alkyl, fluoroalkyl or optionally substituted aryl,the method comprisingstep A of reacting a compound of formula (2): wherein R1 and R2 are as defined above, with carbon monoxide and an alcohol of the formula R3-OH (3)wherein R3 is as defined above, in the presence of a base and a transition metal complex catalyst containing a diphosphine compound having, on each phosphorus atom, at least one substituent selected from alkyl and cycloalkyl groups to obtain the compound of formula (1) above (JP-A-2015-143199). Summary of Invention Technical Problem However, further novel production methods are always in demand. In particular, it would be beneficial to provide a method that is capable of producing an α-fluoroacrylic acid ester compound at a high starting material conversion and high yield by using a small amount of a catalyst. Solution to Problem The present inventors found that a compound an α-fluoroacrylic acid ester compound of formula (1), or a salt thereof: wherein R1, R2 and R3o are as defined later herein is obtained at a high starting material conversion and high yield by reacting a compound of formula (2): wherein R1 and R2 are the same as in formula (1),with carbon monoxide and an alcohol of the formula R3o-OH (3) wherein R3o is the same as in formula (1),in the presence ofpalladium,a double bond-containing compound (α) of formula (α): whereinRb1, Rb2, Yb1, Yb2 and Lb are as defined later herein, anda base, with the proviso that the palladium, taken together with the double bond-containing compound (α) or the diphosphine compound (β), or with both, may form a palladium complex (A). The present invention has thus been completed. More specifically, the present invention provides a method for producing a compound of formula (1) or a salt thereof: wherein R1, R2each independently are H, halogen, alkyl, fluoroalkyl, or optionally substituted aryl;R3ois H or R3; andR3is alkyl, fluoroalkyl or optionally substituted aryl; comprising step A of reacting a compound of formula (2) with carbon monoxide and an alcohol of formula (3): R3-OH (3) wherein R1-R3 are as defined above, in the presence of palladium,a double bond-containing compound (α) of the formula wherein Rb1is H or C1-6-alkyl,Rb2is H or C1-6-alkyl,Yb1is =O or =CH-Ryb1,yb2is -H, =O or =CH-Ryb2, Ryb1 and Ryb2 each independently are C6-14-aryl, or Ryb1 andRyb2 may together form -Ly-, wherein Ly is linear C1-2-alkanediyl optionally having one or more methyl side chains,Lbis a bond, C1-3-alkanediyl, or -C(=O)-,a diphosphine compound (β) having, on each phosphorus atom, at least one substituent selected from alkyl and cycloalkyls, anda base, with the proviso that, in the reaction, the palladium, together with the compound of formula (2), the compound (α), the compound (β), or carbon monoxide, or with one or more of these, may form a palladium complex (A),to obtain the compound represented by formula (1) or a salt thereof;wherein the amount of the palladium complex (A) is ≤ 0.00025 mol per mole of the compound of formula (2). Preferred embodiments of the invention are as defined in the appended dependent claims and/or in the following detailed description. Advantageous Effects of Invention The present invention provides a novel method for producing an α-fluoroacrylic acid ester compound (also referred to as "the present method" hereinafter). In particular, according to the present method, an α-fluoroacrylic acid ester compound can be suitably obtained at a high starting material conversion and a high yield by using a small amount of catalyst. Description of Embodiments 1. Terms The steps, treatments, or operations described in the present specification may be performed at room temperature, unless otherwise specified. In the present description the following definitions apply. The term "Cn-m" (wherein n and m each represent a number) indicates that the number of carbon atoms is n or more and m or less, as a person skilled in the art would usually understand. Examples of "hydrocarbon group" include aliphatic hydrocarbon groups optionally substituted with at least one aromatic hydrocarbon group (e.g., benzyl group) and aromatic hydrocarbon groups optionally substituted with at leas