Bromomethyl 4-methoxyphenyl ketone → HCID 66967157, compound

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Reaction Steps

In this example, heterocylic-protected glycine is synthesized by first forming an Nα-(auxiliary group)-substituted glycine, followed by deprotection and then cyclization by reaction with formalehyde. Triphenylmethyl mercaptan (Aldrich), 4 mmol, and 4′-methoxy-2-bromoacetophenone (Aldrich), 4 mmol, are dissolved in 2 mL DMF, after which 4 mmol DIEA is added. The mixture is stirred at room temperature for 1 hour, after which it is poured in diluted HCl, extracted with ethylacetate, and dried over sodium sulfate. The resulting oil is dissolved in ethylacetate and precipitated by addition of petroleum ether, which after evaporation gives a white solid, 4′-methoxy-2-(triphenylmethylthio)-acetophenone. This compound, 1.44 mmol, and aminoxyacetic acid, 4.3 mmol, are dissolved in 20 mL of trimethylorthoformate (TMOF), after which 0.047 mL of methanesulfonic acid is added as a catalyst. After incubation at room temperature for 48 hours, the solvent is evaporated and the residue taken up in ethylaceetate, washed with 1M monohydrogenpotassium sulfate and dried over sodium sulfate, after which the crude product is purified with silica gel chromatography and an oxime complex is isolated. 0.556 mmol of the oxime complex is dissolved in 2 mL of tetrahydrofuran (THF) and 1.67 mL of 1 M BH3/THF complex is added. After 24 hours, 3 mL of water and 1.5 mL of 10 N sodium hydroxide is added and the mixture is refluxed for 1 hour, after which the mixture is extracted with ethylacetate (4×) and dried over sodium sulfate. The final product of 1-amino-1-(4-methoxyphenyl)-2-(triphenylmethylthio)-ethane, is purified using silica gel chromatography. The 1-amino-1-(4-methoxyphenyl)-2-(triphenylmethylthio)-ethane is then reacted with BrNα-glycine in the presence of a base to give the Nα-(auxiliary group)-substituted glycine, preferably attached to a solid phase support. After deprotecting the sulfhydryl of this compound by treatment with TFA/TIS as described above, the cyclization reaction is carried out by treatment with formaldehyde. The final product is cleaved from the solid phase support by conventional means.

Provenance & Evidence