(3-chloro-2,2-dimethyl-3-oxopropyl) nitrate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 5.2 g of 2,2-dimethyl-3-nitroxypropanoyl chloride in 100 ml of tetrahydrofuran was added at 0° C. under nitrogen to a solution of 6.0 g of 4-carboxy-2-phenylthiazolidine and 4.0 g of potassium carbonate in a mixture of 50 ml of tetrahydrofuran and 150 ml of water. After stirring the resulting solution for 45 minutes the mixture was concentrated under reduced pressure to about 150 ml and then acidified to pH=2 with citric acid. The resulting mixture was extracted with diethyl ether and the organic phase was dried over sodium sulphate and evaporated. The residue was purified by chromatography (silica, petroleum ether 60-80: ethyl acetate: acetic acid/8:8:1). Yield 38%. Empirical formula C15H18N2O6S. Molecular weight 354. Melting point 35°-38° C. TLC system: petroleum ether 60-80: ethyl acetate: acetic acid/4:4:1. Rf 0.50. was concentrated under reduced pressure to about 150 ml The resulting mixture was extracted with diethyl ether the organic phase was dried over sodium sulphate evaporated The residue was purified by chromatography (silica, petroleum ether 60-80: ethyl acetate: acetic acid/8:8:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1.4 g. 2,2-dimethyl-3-nitroxypropanoyl chloride in 50 ml. dry tetrahydrofuran is added dropwise at ambient temperature to a solution of 2.3 g. 3-(2-amino-1,1-dimethylethylamino)-1-(3-methylbenzimidazol-4-yloxy)-propan-2-ol in 150 ml. dry tetrahydrofuran, followed by further stirring for 2 hours. The reaction mixture is evaporated and chromatographed on silica gel with methylene chloride/methanol (4:2 v/v). The product obtained (2.0 g.) is dissolved in 60 ml. methylene chloride and mixed with 0.54 g. fumaric acid in 100 ml. acetone. The precipitate which separates out after the addition of 200 ml. diethyl ether is filtered off with suction and dried. There are obtained 2.3 g. (53% of theory) of the desired product in the form of crystals; m.p. 187°-190° C. The reaction mixture is evaporated chromatographed on silica gel with methylene chloride/methanol (4:2 v/v) The product obtained (2.0 g.) is dissolved in 60 ml after the addition of 200 ml diethyl ether is filtered off with suction dried There are obtained 2.3 g