Tert-Butyl 2-(tert-butyldimethylsilyl)-2-oxoacetate

Abstract

[tert-Butyl 2-(tert-butyldimethylsilyl)-2-oxoacetate] [852447-17-7] C12H24O3Si (MW 244.40) InChI = 1S/C12H24O3Si/c1-11(2,3)15-9(13)10(14)16(7,8)12(4,5)6/h1-8H3 InChIKey = GGYHTNUVBJRLDM-UHFFFAOYSA-N (reagent used in various multicomponent coupling reactions typically for the synthesis of substituted glycolic acid derivatives) Physical Data: bright yellow oil. Solubility: soluble in most organic solvents. Form Supplied in: bright yellow liquid. The most common impurity is silanol remaining from the final oxidation step. Analysis of Reagent Purity: Rf: 0.49 (25% Et2O/Petroleum Ether); IR (thin film) cm−1 2931, 2860, 1716, 1657, 1464, 1369, 1252, 1159, 993, 841, 785; 1H NMR (300 MHz, CDCl3) δ: 0.27 (s, 6H), 0.96 (s, 9H), 1.55 (s, 9H); 13C NMR (75 MHz, CDCl3) δ: −6.6, 17.1, 26.6, 28.1, 83.6, 163.0, 232.9; Anal. Calcd. for C12H24O3Si: C, 58.97; H, 9.90. Found: C, 58.81; H: 9.98. Preparative Methods: the reagent is prepared2 by a three-step sequence starting from commercially available t-butyl acetoacetate. Treating t-butyl acetoacetate with p-acetamidobenzenesulfonyl azide (1.0 equiv), tetrabutylammonium bromide (0.02 equiv), and sodium hydroxide (2.8 equiv) yields the requisite diazoacetate as yellow oil. A silylation is performed on the unpurified diazoacetate with the desired silyl triflate (1.2 equiv) in the presence of Hunig's base (1.2 equiv) to provide the silyl diazoacetates as yellow oils for a series of silyl triflates (TMS, TES, TBS, TBDPS). It is typically most convenient to proceed without purification after the C-silylation, since impurities are more easily rejected after the final step. Oxo transfer to the silyl diazoacetate is mediated by dimethyldioxirane formed in situ3 from Oxone® and acetone to provide the silyl glyoxylate as a yellow oil. The product is purified by flash chromatography in yields typically around 50% for the three-step sequence. This method allows for preparative quantities of silyl glyoxylates with varied silyl functionalities to be prepared. Other methods exist,4 but this preparation of silyl glyoxylates appears to be the most widely applicable at this time. Silyl glyoxylates with a benzyl ester (3)5 or an allylic ester6 functionality can be prepared by a modified procedure. Purification: the final step in the protocol is an Oxone oxidation of the diazoacetate after which the product is purified by flash chromatography eluting with 5% EtOAc/hexanes. Since the product is yellow, the progress of elution can be visually monitored. No purification of the intermediates from the first two steps of the synthesis is required. Handling, Storage, and Precautions: silyl glyoxylates can be stored for several months without significant decomposition if stored in a freezer away from light. The reagents decompose upon prolonged exposure to light and should be wrapped in aluminum foil. These reagents typically are stored at 0 °C to prevent thermal decomposition. The reagent is somewhat volatile and some may be lost by prolonged exposure to high vacuum (particularly the TMS silyl glyoxylates). Silyl glyoxylate toxicity has not been evaluated, but the reagents should be used with common precautions to limit exposure. [852447-25-7] C12H24O3Si (MW 244.40) InChI = 1S/C12H24O3Si/c1-7-16(8-2,9-3)11(14)10(13)15-12(4,5)6/h7-9H2,1-6H3 InChIKey = UEYABJBDWBGSNH-UHFFFAOYSA-N [443988-56-5] C15H22O3Si (MW 278.42) InChI = 1S/C15H22O3Si/c1-15(2,3)19(4,5)14(17)13(16)18-11-12-9-7-6-8-10-12/h6-10H,11H2,1-5H3 InChIKey = XVYKODFPDWKLLK-UHFFFAOYSA-N