Sodium Bicarbonate → (2-Amino-5-cyano-phenyl)-(5-morpholin-4-ylmethyl-pyridin-2-yl)-acetic acid ethyl ester

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Reaction Steps

(5-Cyano-2-nitro-phenyl)-(5-morpholin-4-ylmethyl-pyridin-2-yl)-acetic acid ethyl ester hydrochloride salt (100 g, 223.7 mmol) was slurried in toluene at room temperature and a solution of sodium hydrogen carbonate (47 g, 559 mmol) in water (500 ml) was added and the reaction mixture stirred at room temperature for 45 mins. The organic phase was separated and washed twice with water (500 ml) then concentrated by distillation under vacuum to 229 ml. Dimethylformamide (846 ml) was then added followed by Degussa® [CF1082 RV/W®; Platinum (3%) and Vanadium (0.6%)] on active carbon (20 g, 20 w/w %) and the reaction mixture degassed with nitrogen followed by heating to 40° C. then hydrogen (g) was added to a pressure of 3-4 bar g and left for 30 min then heated to 70° C. and stirred for 6 hrs under an atmosphere of hydrogen. After cooling to room temperature the reaction mixture was purged with nitrogen and the catalyst filtered off and the filtrate concentrated to 395 ml. (The solution was used in the next step; Example 12). An aliquot was taken out and purified by column chromatography on silica eluting with dichloromethane/methanol (1% ammonium hydroxide) (25:1) gave (2-Amino-5-cyano-phenyl)-(5-morpholin-4-ylmethyl-pyridin-2-yl)-acetic acid ethyl ester as a pale orange oil.

Provenance & Evidence