Patent ID: 8691803

Claim:
A process for manufacturing a compound of formula II, or its pharmaceutically acceptable salt, hydrate or solvate without lyophilizing; wherein, R 1 is 1-hydroxyethyl, 1-fluoroethyl, or hydroxymethyl; R 2 and R 3 are independently hydrogen, or C 1 -C 6 alkyl; R 4 and R 5 are independently hydrogen, C 1 -C 6 alkyl, or alkali-metal or alkali earth-metal wherein the alkali-metal or alkali earth-metal is sodium, potassium, lithium, cesium, rubidium, barium, calcium or magnesium; R 6 and R 7 are independently hydrogen, halo, cyano, nitro, hydroxy, carboxy, amino, C 1 -C 6 alkylamino, di C 1 -C 6 alkylamino, C 1 -C 6 alkoxy, C 1 -C 6 alkoxycarbonyl, amino sulphonyl, C 1 -C 6 alkylaminosulphonyl, di-C 1 -C 6 alkylaminosulphonyl, carbamoyl, C 1 -C 6 alkylcarbamoyl, trifluoromethyl, sulphonic acid, C 1 -C 6 alkanoylamino, C 1 -C 6 alkanoyl(N—(C 1 -C 6 )-alkyl)amino, C 1 -C 6 alkanesulphonamido, C 1 -C 6 alkyl-S(O) n wherein n is 0-2; and R 8 is hydrogen, sodium, potassium, lithium, cesium, barium, rubidium, calcium or magnesium; consisting of: (a) dissolving a carbonate source and a base in a diluent to form a first solution at a temperature from 0° C. to 25° C., wherein a mole ratio of the carbonate source to a compound of formula I is 0.5 to 1.5, and a mole ratio of the base to the compound of formula I is 0 to 0.7; Or its pharmaceutically acceptable salt, hydrate or solvate, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are defined as the compound of formula II; (b) mixing the compound of formula I with the first solution at a temperature from −5° C. to 25° C. to form a solution of the compound of formula I, a portion of the base was added into the solution of the compound of formula I to maintain pH at 6.5 to 8.5; and (c) mixing the solution of the compound of formula I with an organic anti-solvent under stirring to crystallize a compound of formula II or its pharmaceutically acceptable salt, hydrate or solvate, wherein the total volume of the organic anti-solvent is 15 to 40 times the solution of the compound of formula I, and the organic anti-solvent is selected from the group consisting of methanol, ethanol, 1-propanol, isopropyl alcohol, 1-butanol, sec-butanol, methyl acetate, methyl ethyl ketone, tetrahydrofuran (THF), isopropylamine (IPA), maleic anhydride, ether, ethyl acetate (EA), isopropyl acetate (IPAc), (di)isopropyl ether (IPE), methyl t-butyl ether (MTBE) and a mixture thereof.