Benzyl chloroformate → Benzyl [2-(4-hydroxy-2-oxo-2,3-dihydro-1,3-benzothiazol-7-yl)ethyl](1-methyl-2-oxoethyl)carbamate

Participants

Reaction Steps

Sodium bicarbonate (1.16 g) was added to a solution of 7-(2-amino-ethyl)-4-hydroxy-3H-benzothiazol-2-one hydrobromide (4.0 g) in water (30 mL) and THF (60 mL), and the mixture was stirred for 15 min. Acetic acid (1.57 mL) was added, followed by 1,1-dimethoxyacetone (1.98 mL) and the mixture was stirred for 30 min. The reaction was then cooled in ice and sodium cyanoborohydride (1.73 g) was added in portions over 10 min. The reaction mixture was stirred for three days, then EtOAc (100 mL) and a solution of NaHCO3 (3.46 g) in water (50 mL) was added and the mixture stirred vigorously. Benzyl chloroformate (1.45 mL) was added and after 3 h a further portion of benzyl chloroformate (0.725 mL) was added. After 2 h the organic phase was separated, washed with water, then 0.1M HCl, water and brine. The resulting solution was evaporated and the residue was redissolved in acetone (75 mL), 2M HCl (50 mL) was added and the mixture was stirred for 2 days. The acetone was evaporated, and the aqueous was extracted into EtOAc. The organic phase was washed with brine, dried and evaporated affording an off-white foam (5 g). LC-MS showed the major component was a mixture of desired aldehyde and the corresponding hydrate (M+H 419/401). The crude aldehyde was used directly in the next step

Provenance & Evidence