反应详情

温度

-6 °C

To a solution of 0.161 ml (1.84 mmol, 1.15 eq.) of oxalyl chloride in 9 ml dichloro-methane at −50 to −60° C. was added a solution of 0.272 ml (3.83 mmol, 2.4 eq.) dimethyl-sulfoxide in 1.5 ml dichloromethane within 5 min. The solution was stirred for 5 min and a solution of 0.457 g (1.60 mmol) of (R)-4-(3-hydroxy-propyl)-2-methyl-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester (example 1B) in 4.5 ml dichloromethane was added within 5 min. The mixture was stirred for 15 min and 1.11 ml (7.98 mmol, 5 eq.) of triethylamine was added within 5 min. The suspension was stirred for 3.5 h and slowly warmed to −6° C. The reaction was neutralized with cold 10% aq. potassium dihydrogenphosphate solution (adjusted with solid potassium dihydrogenphosphate to pH 4-5) and extracted with ethyl acetate (3 times). The organic phases were washed with fresh sat. aq. sodium hydrogencarbonate solution and 10% aq. sodium chloride solution, dried over Na2SO4 and evaporated to give 0.418 g (92%) of the title compound as colorless oil. MS: 285.1 (MH+).

1. stirringThe mixture was stirred for 15 min
2. stirringThe suspension was stirred for 3.5 h
3. extractionextracted with ethyl acetate (3 times)
4. washThe organic phases were washed with fresh sat. aq. sodium hydrogencarbonate solution and 10% aq. sodium chloride solution
5. dry with materialdried over Na2SO4
6. customevaporated