2-Thienylacetyl chloride

Aminocephalosporanic acid (5.00 g) which passed through a 100-mesh sieve was suspended in boiling ethyl acetate (200 ml), and 2-thienylacetyl chloride (Cagniant, Bull. Soc. Chim. France, 1949,847) (4.42 g, 1.5 equiv.) was added in ethyl acetate (20 ml). The mixture was boiled under reflux for 40 minutes, cooled, and filtered. Aniline (5.03 ml) was added, and after 1 hour the mixture was extracted with 3% sodium hydrogen carbonate solution (1 x 150 ml, 2 X 100 ml, 1 x 50 ml) and the alkaline extracts washed with ethyl acetate (3 x 100 ml). The aqueous solution was acidified to pH 1.2, and extracted with ethyl acetate (2 x 150 ml). The ethyl acetate extract was washed with water (4 x 40 ml), dried (MgS04), and concentrated in vacuo to low volume. The crude 7-2 -thienylacetamidocephalosporanic acid (2.5 g) which separated was collected by filtration. Evaporation of the filtrate gave a further 2.68 g (71%) of the product, which was purified by crystallization from ethyl acetate, then aqueous acetone, MP 150°Cto 157°C (decomp.). 

Thienylacetamido)cephalosporanic acid sodium salt may be produced from 2-thienylacetyl chloride, obtainable by treatment of 2-thienylacetic acid [Ernst, Berichte, 19 (1886) 3281] with thionyl chloride in a conventional manner. The 2-thienylacetyl chloride is then reacted with 7-aminocephalosporanic acid and then converted to the sodium salt using sodium hydroxide. 

Table 1 Selected Step 2 intermediates prepared by condensing 3-bromo-2-thienylacetyl chloride with a primary amine...

Scheme 2.3 Reagents (a) C3H7NH2, CH2C12 (b) BH3.Me2S, THF (c) 2- or 3-thienylacetyl chloride, CH2C12, Et3N.

N- -Propyl-3-thiophen-2-yl-acetamide. To a solution of -propylamine (5.9 g, 100 mmol) in dichloromethane (50 mL) and 2N NaOH (10 mL) was added dropwise 3-thienylacetyl chloride 46 (2.8 g, 17.4 mmol) dissolved in dichloromethane (10 mL). The reaction mixture was stirred for 2h at RT. The two layers were separated and the aqueous layer was extracted with dichloromethane (20 mL). The combined organic layers were washed with brine, dried over Na2S04 and concentrated under reduced pressure to yield 2.3 g (72 %) oil which solidified upon standing which was recrystallized from ethyl acetate-hexane JH NMR (CDC13) 8 0.8 (t, 3H, J =... 

Reagents i, Mel ii, NaCHaCOCl-EtsN iii, CU iv, HOCHaCOCHaOAc-AgBF v, NaH-DME vi, separate the isomers vii, Hj-Pd/C viii, thienylacetyl chloride... 

Cefalotin Cefalotin, (6/ -frfl )-3-[(acetyloxy)methyl]-8-oxo-7-[(2-thienylacetyl) amino]-5-thia-l-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.1), is synthesized by direct interaction of 2-thienylacetic acid chloride with 7-aminocephalosporanic acid in the presence of sodium bicarbonate [70-74]. 

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