Malonic acid di-salts and a method for preparing malonyl dihalides

A method for preparing a compound of Formula 1

• wherein
• R1 is phenyl optionally substituted with Q and up to 3 substituents independently selected from R2;
• each R2 is independently halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy or C1-C4 haloalkoxy;
• Q is pyridinyl optionally substituted with up to 2 substituents independently selected from halogen and C1-C4 haloalkyl;
• and
• X is Cl or Br
• comprising contacting a compound of Formula 2
• wherein
• R1 is phenyl optionally substituted with Q and up to 3 substituents independently selected from R2;
• each R2 is independently halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy or C1-C4 haloalkoxy;
• Q is pyridinyl optionally substituted with up to 2 substituents independently selected from halogen and C1-C4 haloalkyl;
• and
• each MA and MB is independently Li, Na, K, NH4, NH(CH2CH3)3, NH(CH2CH2CH2CH3)3, NH2(Bn)2, NH2(cyclohexyl)2 or NH2(phenyl)2,
• with a halogenating agent,
• wherein the halogenating agent is oxalyl chloride, thionyl chloride, phosgene, triphosgene, cyanuric chloride, phosphorous oxychloride, phosphorous trichloride, phosphorous pentachloride, diphosgene, sulfuryl chloride, thionyl bromide, triphenylphosphine dibromide or phosphorous tribromide.

A method of preparing a compound of Formula 4

• wherein
• R1 is phenyl optionally substituted with Q and up to 3 substituents independently selected from R2;
• each R2 is independently halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxv or C1-C4 haloalkoxy;
• Q is pyridinyl optionally substituted with up to 2 substituents independently selected from halogen and C1-C4 haloalkyl;
• R3 is thiazolyl or pyrimidinyl, each optionally substituted with halogen or C1-C2 alkyl;
• and
• R4 is H or C1-C4 alkyl;
• comprising preparing a compound of Formula 1
• wherein
• R1 is phenyl optionally substituted with Q and up to 3 substituents independently selected from R2;
• each R2 is independently halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy or C1-C4 haloalkoxy;
• Q is pyridinyl optionally substituted with up to 2 substituents independently selected from halogen and C1-C4 haloalkyl;
• and
• X is Cl or Br
• by contacting a compound of Formula 2
• wherein
• R1 is phenyl optionally substituted with Q and up to 3 substituents independently selected from R2;
• each R2 is independently halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy or C1-C4 haloalkoxy;
• Q is pyridinyl optionally substituted with up to 2 substituents independently selected from halogen and C1-C4 haloalkyl;
• and
• each MA and MB is independently Li, Na, K, NH4, NH(CH2CH3)3, NH(CH2CH2CH2CH3)3, NH2(Bn)2, NH2(cyclohexyl)2 or NH2(phenyl)2;
• with a halogenating agent
• wherein the halogenating agent is oxalyl chloride, thionyl chloride, phosgene, triphosgene, cyanuric chloride, phosphorous oxychloride, phosphorous trichloride, phosphorous pentachloride, diphosgene, sulfuryl chloride, thionyl bromide, triphenylphosphine dibromide or phosphorous tribromide;
• to produce a compound of Formula 1;
• and
• reacting a compound of Formula 5
• wherein
• R3 is thiazolyl or pyrimidinyl, each optionally substituted with halogen or C1-C2 alkyl;
• and
• R4 is H or C1-C4 alkyl;
• with the compound of Formula 1 to prepare the compound of Formula 4.