Berrchem API introductions

The in-house development and production of various multi-customer active pharmaceutical ingredients is one pillar of BerrChem's API business model. A product list of currently offered generic APIs is available and information about new products under the development and/or evaluation can be provided upon request.

From simple, single-step reactions to more complex, difficult multi-step reactions and everything in between, BerrChem can handle your individual requirements for the good cooperation with the top chemical scientists in China. We offer starting materials, intermediates, reference compounds, and derivatives of lead compounds in scales ranging from grams to hundreds of kilograms and tons.For Example:

5,5-Dimethylthiazolidine-4-carboxylic acid (I) is protected as the N-Boc derivative (II), and subsequently treated with allyl bromide (III) and triethylamine to form the allyl ester (IV). Acidic Boc group cleavage in (IV) provides amino ester (V), which is further coupled to the lactone acid (VI) to furnish amide (VII). The allyl ester group of (VII) is then removed by treatment with morpholine and Pd(PPh3)4, yielding acid (VIII). This is then coupled to (3,5-dimethylisothiazol-4-yl)methyl amine (IX) employing EDC/HOAt to afford the corresponding amide (X). Lactone ring opening in (X) by hydrolysis with LiOH gives rise to the hydroxy acid (XI), which is further protected as the silyl ether (XII) employing t-butyldimethylsilyl triflate.

For Example:
2,6-Dichlorobenzenethiol (I) is oxidized to the sulfonyl chloride (II) employing N-chlorosuccinimide. Subsequent treatment of acid chloride (II) with ammonia in cold pyridine provides sulfonamide (III). Reaction of (III) with HNO3 in the presence of concentrated H2SO4 leads to the nitro derivative (IV). Then, displacement of one chloride group of (IV) with potassium acetate in the presence of crown ether gives rise to the acetate ester (V), which is further hydrolyzed to phenol (VI) under acidic conditions. Nitro group reduction in (VI) with H2 and Pd/C affords aniline (VII). Finally, coupling of (VII) with 2,3-dichlorophenyl isocyanate (VIII) produces the title diaryl urea.

Example 1 of BerrChem Intermediate PRODUCTS

The cyclization of benzaldehyde (I) with methyl 4-nitrobutyrate (II) and ammonium acetate in refluxing acetic acid gives 5-nitro-6-phenylpiperidone (III), which is treated with ozone and t-BuOK in dichloromethane/methanol to yield 2-phenylpiperidine-3,6-dione (IV). The reduction of (IV) by means of LiAlH4 in THF affords 2-phenylpiperidin-3-ol (V) as a mixture of cis- and trans-isomers. The reaction of (V) with TsOH, followed by crystallization in methanol/ethyl acetate provides the corresponding tosylate (VI) as the (rac)(cis)-isomer. The neutralization of the tosylate (VI) with Na2CO3 in ethyl acetate/water gives 2-phenylpiperidin-3-ol (VII) as a racemic cis mixture, which is submitted to optical resolution with (+)-dibenzoyltartaric acid to yield (+)(cis)-(VIII). The reaction of (VIII) with Boc2O affords the N-protected compound (IX), which is alkylated with 3,5-bis(trifluoromethyl)benzyl bromide (X) and NaH to provide the benzyl ether (XI). Finally, this compound is N-deprotected by means of TFA to obtain the target piperidine.

Example 2 of BerrChem Intermediate PRODUCTS