A general procedure for the base-promoted hydrolysis of hindered esters at ambient temperatures

Abstract

Recently, we reported that essentially "anhydrous hydroxide" was an excellent reagent for the hydrolysis of tertiary amides at ambient temperatures.1 This reagent was generated via the reaction of 2 equiv of potassium tert-butoxide with 1 equiv of water.2 Mechanistically, it appeared that the relatively unsolvated hydroxide added to the tertiary amide, 1, to produce 2. Removal of a hydroxylic proton from 2 would then produce the dianion, 3. Fragmentation of 3 then produced the most stable pair of anions, which in this case was 4 and 5. Utilizing this concept, a series of tertiary amides was

On designing non-saccharide, allosteric activators of antithrombin

“…It is possible that the presence of naked carboxylic acid functionality under microwave conditions induces degradation of organic sulfates resulting in multiple products. To circumvent this problem, the carboxylic acid ester in IES 4 and IES 5 was hydrolyzed in excellent yields by simply stirring with KBuO- t /H 2 O (2:1) in anhydrous DMSO at RT 16. It is worthwhile to mention that this hydrolysis fails miserably when standard saponification conditions (NaOH/water) are used.…”

“…Briefly, each ester (0.03 – 0.08 mmol) was stirred with potassium t -butoxide and H 2 O (2:1 molar equivalent, 3 equiv. KBuO- t ) in DMSO (0.1 M) under nitrogen at room temperature until the starting material was consumed (HPLC analysis, 1–3 h),16 after which sodium dibasic phosphate (10 equiv) in H 2 O (2 mL) was added to the reaction mixture. Following 15 min of stirring, the reaction mixture was loaded onto a Sephadex G10 column (160 cm) and chromatographed using water as an eluent.…”

Design, synthesis, and evaluation of 4- and 5-substituted o-(octanesulfonamido)benzoic acids as inhibitors of glycerol-3-phosphate acyltransferase

“…Alternatively, coupling of 4 and 5 with various trans -arylvinyl boronic acids under an argon atmosphere provided vinyl-linker precursors 10a–b and 11a–b . Each of the benzoates was then hydrolyzed, either under Gassman conditions 15 or in aqueous 1 M NaOH, to afford analogs 12a–l, 13a–l, 14a–b, 15a–d, 16a–b and 17a–b . Alternatively, hydrogenation of 10a–b and 11a–b prior to hydrolysis afforded ethyl-linked analogs 18a–b and 19a–b .…”

Polynorbornene-based Template for Polymer Synthesis

“…Throughout this study, polynorbornene or polycyclobutene skeleton are adopted as the template for polymer synthesis. gives the unsymmetrical ladderphane 23 which is then hydrolyzed using anhydrous hydroxide conditions 41 to afford the linker 24 and the daughter polymer 20. The crude polymer 20 was treated in situ with CsF and MeI 42 to give the corresponding methyl ester 25.…”