chloromethyl morpholine-4-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloromethyl morpholine-4-carboxylate [6316] (0.3 g, 1.67 mmol, 1.0 eq) and lithium bromide (0.72 g, 8.3 mmol, 5.0 eq) was taken in acetonitrile (10 ml). The reaction was refluxed at 90° C. for 30 h. Reaction progress was monitored by TLC/1H NMR. The reaction was filtered off and filtrate was evaporated to dryness under reduced pressure to yield light brown gel, bromomethyl morpholine-4-carboxylate [6327](0.30 g, 80%) Reaction progress The reaction was filtered off filtrate was evaporated to dryness under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloromethyl morpholine-4-carboxylate [285] (0.3 g, 1.67 mmol, 1.0 eq) and sodium bromide (0.86 g, 8.3 mmol, 5.0 eq) was taken in acetone (10 ml). The reaction was refluxed at 60° C. for 24 h. Reaction progress was monitored by TLC/1H NMR. The reaction was filtered off and filtrate was evaporated to dryness under reduced pressure to yield light brown gel, bromomethyl morpholine-4-carboxylate [286] (0.30 g, 80%) Reaction progress The reaction was filtered off filtrate was evaporated to dryness under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloromethyl morpholine-4-carboxylate (1 equiv.) is added to a 0.1M solution of the potassium salt of methacrylic acid (1.1 equiv.) and 18-crown-6 (2/100 equiv.) in DMF at 0° C. After 15 min at 0° C. and a suitable time at elevated temperature the reaction mixture is filtered and concentrated to dryness under reduced pressure. The residue is purified by flash chromatography giving the wanted methacryloyloxymethyl morpholine-4-carboxylate. a suitable time at elevated temperature the reaction mixture is filtered concentrated to dryness under reduced pressure The residue is purified by flash chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Morpholine (1 equiv.) is slowly added to a 0.1M solution of chloromethyl chloroformate (10 equiv.) in methylene chloride at low temperature. After 15 min at low temperature and a suitable time at 25° C. the reaction mixture is filtered and concentrated to dryness under reduced pressure. The residue is purified by flash chromatography giving chloromethyl morpholine-4-carboxylate. a suitable time at 25° C. the reaction mixture is filtered concentrated to dryness under reduced pressure The residue is purified by flash chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using 5-chloro-2-hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]benzamide 1 sodium salt (compound of Example 43(1)) and 4-[(chloromethoxy)carbonyl]morpholine as the raw materials, the same operation as the Example 98 gave the title compound.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using chloroformic acid chloromethyl ester and morpholine as the raw materials, the same operation as the Example 101(1) gave the title compound as a crude product, and the crude product was used for the next reaction without further purification.