Phenol → Methyl 2-[2-(morpholin-4-ylmethyl)-5-ethylphenoxy]propanoate

Participants

Reaction Conditions

Reaction Steps

To a 200 gallon reactor was added 582 pounds (%Wt/Wt Phenol to Solvent--14.1%) of acetonitrile, followed by 82 pounds (0. 323 mole--1.0 equiv.) of 87% pure 2-(morpholin-4-ylmethyl)-5-ethylphenol, 72.4 pounds (0.717 mole--2.22 equiv.) of triethylamine, and 99.0 pounds (0.717 mole--2.22 equiv.) of potassium carbonate. The mixture was heated to 70° C., and 90.1 pounds (0.539 mole--1.67 equiv.) of methyl 2-bromopropanoate was added during a two hour period a rate to maintain the reaction temperature at 65-70° C. Upon completion of addition, the reaction mixture was stirred at to 65-70° C. for seven hours. After this time, the reaction mixture was analyzed by GC, which indicated that 8% of the phenol starting material remained. An additional 9.0 pounds (0.054 mole--0.16 equiv.) of methyl 2-bromopropanoate, 8.0 pounds (0.058 mole--0.17 equiv.) of potassium carbonate, and 4.0 pounds (0.040 mole--0.12 equiv.) of triethylamine were added. Upon completion of addition, the reaction mixture is stirred at 65-70° C. for an additional hour. At the conclusion of this period, the reaction mixture is filtered, and the filtrate was concentrated under vacuum at 70° C. to yield an oil. The oil was taken up in 213 pounds of toluene and 185 pounds of a 2.5% aqueous sodium carbonate solution. The organic layer is separated from the aqueous layer and concentrated under vacuum at 90° C., yielding 106.0 pounds of 86.2% pure methyl 2-[2-(morpholin-4-ylmethyl)-5-ethylphenoxy]propanoate (92% yield).

Provenance & Evidence