Methyl 2-chloro-4-methylbenzo[d]thiazole-5-carboxylate synthesis

Yield:306276-86-8 77%

Reaction Conditions:

with tert.-butylnitrite;sodium chloride;copper(I) chloride in water;ethyl acetate;acetonitrile;

Steps:

1 1.1 Methyl 2-chloro-4-methylbenzothiazole-5-carboxylate

1.1 Methyl 2-chloro-4-methylbenzothiazole-5-carboxylate A solution of 5 g (22.5 mmol) of methyl 2-amino-4-methylbenzothiazole-5-carboxylate in 2 1 of acetonitrile was admixed with 10 ml of water, 4.5 g (44.8 mmol) of copper(I) chloride, 6.6 g of sodium chloride (110 mmol) and 2 ml of 15-crown-5. A solution of 3 g (29 mmol) of tert-butyl nitrite was then added dropwise with stirring, the solution was heated at reflux for 15 h, the resulting precipitate was filtered off and the solution was concentrated under reduced pressure. The residue was then extracted three times with in each case 500 ml of ethyl acetate. To this end, the solvent was heated to boiling point and the solution was filtered whilst hot. The extracts were concentrated under reduced pressure. The residue was purified by trituration with n-hexane/diethyl ether. This gave 4.2 g (17.4 mmol, 77% yield) of methyl 2-chloro-4-methylbenzothiazole-5-carboxylate of m.p. 112° C. ¹H-NMR (CDCl₃): δ (ppm)=2.98 (s, 3H), 3.94 (s, 3H), 7.64 (d, 1H), 7.95 (d, 1H).

References:

US2004/33899,2004,A1