2-[(tert-Butoxycarbonyl)amino]-3-(2-fluoro-4,5-dimethoxyphenyl)-2-propanoic Acid Methyl Ester synthesis

Yield:853759-47-4 100%

Reaction Conditions:

with N,N,N',N'-tetramethylguanidine in chloroform at 20;

Steps:

1.a

Step a: synthesis of 2-tert-butoxycarbonylamino-3-(2-fluoro-4,5-dimethoxyphenyl)-acrylic acid ethyl ester. To a stirred solution of 2-fluoro-4,5-dimethoxy benzaldehyde (1.0 g, 5.4 mmol) and 1,1,3,3-tetramethylguanadine (0.9 g, 8.1 mmol) in chloroform (10 mL) is added tert-butoxycarbonylamino-(dimethoxy-phosphoryl)-acetic acid methyl ester (1.7 g 5.4 mmol) dropwise at room temperature under a N₂ atmosphere. The resulting solution is stirred overnight. The solution is concentrated in vacuo and the resulting product is redissolved in chloroform (20 mL) and ethyl acetate (20 mL) and washed with water (30 mL). The pH is lowered to 6 by the addition of HCl (10% solution). The phases are separated and the organic phase is washed with water (30 mL). The combined aqueous phases are concentrated in vacuo to dryness to afford 2.1 g (100%) of a white solid. ¹H NMR is consistent with theory.

References:

US2005/137421,2005,A1 Location in patent:Page/Page column 5