Esterification with triethyl orthoformate

Scheme 7 Esterification of 1-Aminoalkylphosphonic Acids with Triethyl Orthoformate To Give Diethyl 1-Aminoalkylphosphonate Oxalic Acid Salts 251...

The new pyrazolo[l,5-tf][l,3,5]benzoxadiazocine heterocyclic ring system 123 was prepared by cyclization of 4,5-dihydro-3-methyl-5-(2-hydroxyphenyl)-17/-pyrazole-l-carboximidamide with triethyl orthoformate. A reaction mechanism involving re-esterification of triethyl orthoformate with phenolic hydroxyl of the additional equivalent of hydroxyphenyl pyrazoline was proposed to explain the formation of the product with an additional guanidine moiety (Equation 17 <2002J(P1)1260>). 

Thus, chalcone (26), available via aldol condensation between the appropriate benzaldehyde and acetophenone, was transformed into the 1,3-diarylpropene (27) via a two-step sequence involving ethyl chloroformate and NaBH4, followed by protection of the phenolic hydroxy group as the TBDMS ether. Asymmetric dihydroxylation of olefin (2 7) with AD-mix-a gave an intermediate diol, which was converted into ortho-ester (28) with triethyl orthoformate in the presence of catalytic pyridinium -toluenesulfonate (PPTS), followed by deprotection of the TBDMS ether with TBAF in THE. Treatment of ortho-ester (28) with triethyl orthoformate and PPTS gave an intermediate (27( ,35)- w j -flavan-3-ol formate ester. De-esterification with K2CO3 in THF/methanol and oxidation of the... 

The strategy for the synthesis of phosphinate 54a or 54b involves the activation of the phosphoms atom into the P reactant, followed by successive reactions with a Michael acceptor (ethyl acrylate or diethyl maleate), dibromoethane, and an esterification using triethyl orthoformate. The incorporation of the amino acid group accomplished by nucleophilic substitution of the anion of the diethylaceta-midomalonate yielded the branched phosphinates in 50-77% yield. The final deprotected compounds were obtained in 11-21% yield after acidic deprotection and decarboxylation and they were purified by ion exchange chromatography. Compound 54b was synthesized by alkylation of the phosphonite intermediate with acetamidoacrylic acid, followed by acidic deprotection and ion exchange chromatography purification (Scheme 8). 

Esterification of sulfonic acids.1 Sulfonic acids are converted into methyl or ethyl esters on reaction with trimethyl or triethyl orthoformate. Yields are >80% in esterification of arenesulfonic acids, but are somewhat lower in the reaction of alkanesulfonic acids because of volatility of the products. 

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