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PREPARATION 16 Methyl 4,5-dimethyl-3-methoxythiophene-2-carboxylate To a solution of methyl 3-hydroxy-4,5-dimethylthiophene-2-carboxylate (Preparation 1) (29.7 g, 160 mmol) in anhydrous acetone (500 ml) was added anhydrous potassium carbonate (24.5 g, 178 mmol) and the mixture stirred for 1 hour at room temperature. Dimethyl sulphate (22.4 g, 178 mmol) was added and the mixture stirred under reflux for 2.5 hours. The solvent was evaporated under reduced pressure and the residue partitioned between water and ethyl acetate. The organic phase was washed with brine, dried with sodium sulphate and evaporated to give crude product which was used in the following preparation.
With potassium; In acetone;
PREPARATION 2 Methyl 4,5-dimethyl-3-methoxythiophene-2-carboxylate To a solution of methyl 3-hydroxy-4,5-dimethylthiophene-2-carboxylate (Preparation 1) (29.7 g, 160 mmol) in anhydrous acetone (500 ml) was added anhydrous potassium carbonte (24.5 g, 178 mmol) and the mixture stirred for 1 hour at room temperature. Dimethyl sulphate (22.4 g, 178 mmol) was added and the mixture stirred under reflux for 2.5 hours. The solvent was evaporated under reduced pressure and the residue partitioned between water and ethyl acetate. The organic phase was washed with brine, dried with sodium sulphate and evaporated to give crude product which was used in the following preparation.
PREPARATION 1 Methyl 4,5-dimethyl-3-hydroxythiophene-2-carboxylate Dry hydrogen chloride gas was bubbled through a mixture of ethyl 2-methyl-3-oxobutanoate (7.6 g, 50 mmol) and methyl 2-mercaptoacetate (11.2 g, 100 mmol) at -10 C. until saturated. The oil was allowed to stand for 3 hours at room temperature, diluted with dichloromethane and washed with brine. After drying with sodium sulphate and evaporation of solvent the oil was dissolved in methanol (10 ml) and added dropwise to methanolic potassium hydroxide (2N; 75 ml), stirring at room temperature for 1 hour. The solution was diluted with iced water (125 ml) and acidified with 3N hydrochloric acid at -3 to 0 C. to pH1. The precipitate was filtered and washed with water (5.5 g, m.p. 50-51 C., methanol).
EXAMPLE 2 Methyl 3-hydroxy-4,5-dimethyl-2-thiophenecarboxylate Prepared by the method described in Example 1 from ethyl alpha-methyl acetoacetate (29 g, 0.20 moles), methyl thioglycolate (45 g, 0.40 moles) and sodium (10.2 g, 0.44 moles). Recrystallization from methanol gave the product (15.2 g); mp 52-54 C.
With sodium;
EXAMPLE 2 Methyl 3-hydroxy-4,5-dimethyl-2-thiophenecarboxylate. Prepared by the method described in Example 1 from ethyl alpha-methyl acetoacetate (29 g, 0.20 moles), methyl thioglycolate (45 g, 0.40 moles) and sodium (10.2 g, 0.44 moles). Recrystallization from methanol gave the product (15.2 g); mp 52-54C.
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