Process for preparing large size isoxazoline particles

A process for preparing isoxazoline compound particles wherein the isoxazoline compound is a compound of Formula (I)

• wherein
• R1=halogen, CF3, OCF3, or CN;
• n=integer from 0 up to and including 3;
• m=1 or 2;
• R2=C1-C3 haloalkyl;
• T=ring structure:
• 5-, or 6-membered, or bicyclic, which is optionally substituted by one or more radicals Y;
• Y=methyl, halomethyl, halogen, CN, NO2, NH2—C═S, or two adjacent radicals Y together form a chain;
• Q=X—NR3R4, NR5-NR6—X—R3, X—R3, or a 5-membered N-heteroaryl ring, which is optionally substituted by one or more radicals;
• X=CH2, CH(CH3), CH(CN), CO, or CS;
• R3=hydrogen, methyl, haloethyl, halopropyl, halobutyl, methoxymethyl, methoxyethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, N-phenyl-N-methyl-amino, haloethylaminocarbonylmethyl, haloethylaminocarbonylethyl, tetrahydrofuryl, methylaminocarbonylmethyl, (N,N-dimethylamino)-carbonylmethyl, propylaminocarbonylmethyl, cyclopropylaminocarbonylmethyl, propenylaminocarbonylmethyl, haloethylaminocarbonylcyclopropyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl,
• wherein
• ZA=hydrogen, halogen, cyano, or halomethyl;
• R4=hydrogen, ethyl, methoxymethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, methylcarbonyl, ethylcarbonyl, propylcarbonyl, cyclopropylcarbonyl, methoxycarbonyl, methoxymethylcarbonyl, aminocarbonyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, haloethylaminocarbonylmethyl, cyanomethylaminocarbonylmethyl, or haloethylaminocarbonylethyl;
• R5=H, alkyl, or haloalkyl;
• R6=H, alkyl, or haloalkyl;
• or wherein R3 and R4 together form a substituent selected from the group consisting of:
• or salt or solvate thereof
• comprising
• a) Combining an isoxazoline compound in a crystallizer vessel with a solvent which has a temperature dependent solubility of the isoxazoline compound;
• b) Heating the crystallizer vessel until the isoxazoline compound is dissolved in the solvent;
• c) Cooling the crystallizer vessel to 48-55° C. to form a batch of supersaturated isoxazoline compound in the solvent;
• i) adding crystalline seed of the isoxazoline compound to the crystallizer vessel to initiate crystallization and particle growth;
• ii) Forming a slurry of isoxazoline compound particles and solvent in the crystallizer vessel;
• d) Maintaining the temperature of the crystallizer vessel to 48-55° C.;
• e) Removing a portion of the slurry of isoxazoline compound particles of step cii) and heating the removed portion to fully dissolve the isoxazoline compound particles in the solvent;
• wherein the rate of removal is at a rate of approximately 0.25 to 0.75 batch volumes per hour;
• and wherein the batch volume is the volume of the supersaturated isoxazoline compound solution created in step c);
• f) Returning the dissolved isoxazoline compound solution to the crystallizer vessel;
• wherein the rate of return is equal to the rate of removal of step e);
• and
• g) Cooling the crystallizer vessel to achieve isoxazoline compound particles of the desired dimensions;
• wherein the desired particle dimensions are particles having a volume weighted particle size distribution (d50) as measured by a static light scattering instrument of between 75 and 120 μm and an average particle thickness as measured by scanning electron microscopy (SEM) of greater than 10 μm.