Chloroacetyl chloride → Morpholine, 4-(chloroacetyl)-

Temperature

0 °C

To the solution of morpholine (10 mmol, 0.872 mL) and Et3N (15 mmol, 2.09 mL) in THF (20 mL) at 0° C. was dropped in chloroacetyl chloride 1 (12 mmol, 0.956 mL). The mixture was stirred at 0° C. for 4 h and then r.t. overnight. The reaction was quenched with H2O and evaporated to dryness. Purification by column chromatography (CH2Cl2/CH3OH=50/1) gave 2-chloro-1-morpholin-4-yl-ethanone 2 (1.62 g, 100%). 2 (1.6 g, 0.98 mmol) was treated with piperazine-1-carboxylic acid t-butyl ester (10 mmol, 1.86 g) in DMF (20 mL) at 70° C. for 12 h in the presence of K2CO3 (3 mmol, 4.14 g). Solvents were evaporated and the crude product was purified by flash chromatography (CH2Cl2/CH3OH=30/1) to give 4-(2-morpholin-4-yl oxo-ethyl)-piperazine-1-carboxylic acid t-butyl ester 4, which was treated with TFA (5 mL) in CH2Cl2 (5 mL) at r.t. for 2 h. Evaporation of all solvents furnished the TFA salt of 1-morpholin-4-yl-2-piperazin-1-yl-ethanone 4 (4.1 g, 93%).

1. customr.t. overnight
2. customThe reaction was quenched with H2O
3. customevaporated to dryness
4. customPurification by column chromatography (CH2Cl2/CH3OH=50/1)

ORD record

ord-40bdcf0c0fcd40edbef801ff37d2294b

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06642232B2