Catalytic Synthesis of 3-Alkoxyacrylic Acid Esters Under Neat Conditions

Abstract

Triethylamine or Ph 3 P (0.05 eq.) was found to catalyze the addition of alcohols to alkyl propiolates. The reaction occurred much more rapidly without solvent than in solvent. The E/Z ratio was relative to the reaction temperature. Water was found to inhibit the reaction.

Synthesis of carboxy‐polyethylene glycol‐amine (CA (PEG)n) and [1‐14C]‐CA (PEG)n via oxa‐Michael addition of amino‐polyethylene glycols to propiolates vs to acrylates

“…While the oxa‐Michael addition of an alcohol to propiolate has been reported, to the best of our knowledge, it has not been applied to the synthesis of CA (PEG) n ‐type molecules. To our delight, treatment of compound 11 (1.0 to 1.5 Eq) with 1 Eq of benzyl propiolate ( 18 ) in the presence of N ‐methylmorpholine in CH 2 Cl 2 at room temperature gave adduct 21 smoothly in 89% isolated yield (Scheme ).Dibenzyl 3,3'‐oxy‐diacrylate, formed due to the presence of trace amount of water, was also isolated in 4% yield from the reaction and it was easily removed chromatographically .…”

Lipase Catalyzed Regioselective Lactamization as a Key Step in the Synthesis of N-Boc (2R)-1,4-Oxazepane-2-Carboxylic Acid

“…On a 100 g scale, dibenzylamine was added to neat methyl (2 R )-glycidate 2 at 70 °C, affording a quantitative yield of crude methyl (2 R )-3-(dibenzylamino)-2-hydroxypropanoate 3 . Conjugate addition of 3 to methyl propiolate gave a 93:7 mixture of the E and Z isomers of 4 in 98% overall yield and subsequently, hydrogenation using palladium hydroxide as a catalyst, afforded methyl (2 R )-3-amino-2-(3-methoxy-3-oxopropoxy)propanoate 5 (82% w/w, 87% effective yield) . Upon neat storage we found that the amino diester 5 was unstable and slowly polymerized, but in a solution of, e.g., dioxane or methanol it was stable for weeks at +5 °C.…”