Sulfuryl chloride → Ethyl 2-chloro-o-chlorobenzoylacetate

To a cold (5° C.) mixture at 55.0 g (0.423 mole) of ethyl acetoacetate, 70 ml. of benzene, 18.3 ml. of 33% sodium hydroxide, and 141 ml. of water was added simultaneously with vigorous stirring 80.0 g (0.457 mole) of o-chlorobenzoyl chloride and 76 ml. of 33% sodium hydroxide in 1 hour as described in Example 4. The aqueous solution of sodium salt of ethyl o-chlorobenzoylacetoacetate was stirred with 22.5 g (0.424 mole) of ammonium chloride for 18 hours. The aqueous solution was then saturated with 25.0 g of sodium chloride. At this moment, some precipitate formed which was filtered. The analysis indicated this material was mainly the sodium salt of ethyl o-chlorobenzoylacetoacetate. The sodium salt and the aqueous filtrate were combined and acidified with dilute hydrochloric acid. The oil which separated was extracted with ether. The ether solution was dried (MgSO4) and concentrated under reduced pressure. The residue was Kugelrohr distilled to give 30.0 g of oil which contained mainly ethyl o-chlorobenzoylacetoacetate. This material was stirred with a mixture of 7.2 g of ammonium chloride, 14 ml. of concentrated ammonium hydroxide and 150 ml. of water and worked up as described in Example 4 to give 16.6 g (15%) of crude ethyl o-chlorobenzoylacetate which was about 92% pure. A mixture of 15.0 g (0.065 mole) of ehtyl o-chlorobenzoylacetate, 9.5 g (0.070 mole) of sulfuryl chloride and 20 ml. of chloroform was held at reflux for 6 hours and concentrated to give 17.3 g of crude ethyl 2-chloro-o-chlorobenzoylacetate. A mixture of 17.0 g (0.065 mole) of ethyl 2-chloro-o-chlorobenzoylacetate, 4.94 g (0.065 mole) of thiourea and 65 ml. of ethanol was held at reflux for 2 hours and worked up as described in Example 4 to give 15.0 g of solid, m.p. 114°-136° C. which was recrystallized twice from ethanol to give 5.8 g (31%) of ethyl 2-amino-4-(o-chlorophenyl)-5-thiazolecarboxylate, m.p. 162°-164° C. Part (1.0 g) of this material was recrystallized from toluene to give 0.75 g of pure ethyl 2-amino-4-(o-chlorophenyl)-5-thiazolecarboxylate, m.p. 165°-166° C. A solution of 4.2 g (0.015 mole) of ethyl 2-amino-4-(o-chlorophenyl)-5-thiazolecarboxylate in 50 ml. of 85% phosphoric acid and 15 ml. of nitric acid was diazotized with 1.12 g (0.016 mole) of sodium nitrite as described in Example 4. The diazonium salt solution was poured into a solution of 1.50 g (0.015 mol) of cuprous chloride in 7.5 ml. of concentrated hydrochloric acid and 7.5 ml. of water. The reaction mixture was worked up as described in Example 4 to give 4.0 g of oil which was Kugelrohr distilled (150° C. at 0.3 mm) to give 2.0 g of oil. The material was purified to give 0.66 g (15%) of ethyl 2-chloro-4-(o-chlorophenyl)-5-thiazolecarboxylate as a colorless liquid.

1. temperatureat reflux for 6 hours
2. concentrationconcentrated

ORDレコード

ord-4e584fdd93d940ef9d12fcff8a64a612

出典データセット

uspto-grants-1982_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US04336389