4-Methylmorpholine → HCID 22880227, compound

Temperature

-10 °C

(E)-3-(4-Chloroacetylaminophenyl)acrylic acid (1.44 g, 6.0 mmol) was suspended in 50 ml of tetrahydrofuran, treated with 0.66 ml (6.0 mmol) of N-methylmorpholine and cooled to −10° C. Subsequently, 0.8 ml (6.0 mmol) of isobutyl chloroformate was added dropwise thereto, the mixture was stirred for 30 minutes while cooling and then, at room temperature overnight. The solvent was removed in a vacuum, the residue was taken up in ethyl acetate and extracted twice with water and once with saturated aqueous sodium chloride solution. The organic phase was dried over magnesium sulphate and concentrated. The thus-obtained mixed anhydride was diluted in 25 ml of dichloromethane and added dropwise to a solution of 500 mg (4.5 mmol) of (1S,5R)-2,6-diazabicyclo[3.2.0]heptan-7-one (Example 2) dissolved in 25 ml of dichloromethane and 4 ml of dimethylformamide. The mixture was left to react overnight and the product which separates was filtered off under suction. The latter was purified by chromatography (silica gel, 1. ethyl acetate, 2. ethyl acetate/ethanol=3:2). Yield: 1.0 g (50%).

1. temperaturewhile cooling
2. customat room temperature
3. customovernight
4. customThe solvent was removed in a vacuum
5. extractionextracted twice with water and once with saturated aqueous sodium chloride solution
6. dry with materialThe organic phase was dried over magnesium sulphate
7. concentrationconcentrated
8. additionThe thus-obtained mixed anhydride
9. additionwas diluted in 25 ml of dichloromethane
10. waitThe mixture was left
11. customto react overnight
12. filtrationthe product which separates was filtered off under suction
13. customThe latter was purified by chromatography (silica gel, 1. ethyl acetate, 2. ethyl acetate/ethanol=3:2)

ORD record

ord-b1897cd5723444ebbd0d629e4920cb42

Source dataset

uspto-grants-2003_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06566355B1