Reaction #1178436
ord-f25ca73d403a4fb5a9e4c0b09b5647fa
Reaction equation
Reactants
Reagents
Solvents
Conditions
Workup
- 1Otherthe precipitate formed
- 2Filtrationis filtered off
Procedure
4.1 1.48 ml (19.9 mmol) of 37% aqueous formaldehyde solution are added to a solution of 2.00 g (19.0 mmol) of DL-isoserine in 10 ml of 1N aqueous sodium hydroxide solution. The resultant solution is left at 5° C. for 18 hours. A solution of 3.46 g (19.1 mmol) of 5-chlorothiophenecarbonyl chloride in 10 ml of acetone is added dropwise to this solution at an internal temperature of 0-5° C. During the dropwise addition, the pH is held at a value above 7 by addition of solid sodium hydrogencarbonate. When the addition is complete, the mixture is allowed to warm to room temperature, water is added, and the mixture is extracted with tert-butyl methyl ether. The aqueous phase is acidified using 1N HCl and extracted with tert-butyl methyl ether. This organic phase is dried over sodium sulfate and evaporated, giving 3-(5-chlorothiophene-2-carbonyl)oxazolidine-5-carboxylic acid as a colourless solid; ESI 262. 4.2 479 mg (2.50 mmol) of N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (DAPECI) are added to a solution of 500 mg (1.91 mmol) of 3-(5-chlorothiophene-2-carbonyl)oxazolidine-5-carboxylic acid and 367 mg (1.91 mmol) of 4-(4-aminophenyl)morpholin-3-one in 5 ml of dimethylformamide (DMF), and the mixture is stirred at room temperature for 18 hours. The reaction mixture is added to saturated sodium hydrogencarbonate solution, and the precipitate formed is filtered off, giving N-[4-(3-oxomorpholin-4-yl)phenyl]-3-(5-chlorothiophene-2-carbonyl)oxazolidine-5-carboxamide (“A5”) as a colourless solid; ESI 436.