1,1'-Carbonyldiimidazole → (R,Z)-methyl 4-((tert-butoxycarbonyl)amino)-3-hydroxypent-2-enoate

Participants

Reaction Conditions

Reaction Steps

To a 1-L 3-neck round-bottomed flask, connected to a mechanical stirrer, was added N-Boc-D-alanine (20.00 g, 106 mmol) followed by THF (529 mL). Then 1,1′-carbonyldiimidazole (25.7 g, 159 mmol) was slowly added into the reaction mixture (note: gas evolution was observed). The mixture was stirred under inert atmosphere for 3 h. Then magnesium chloride (20.13 g, 211 mmol), followed by potassium methyl malonate (33.0 g, 211 mmol) were added into the reaction mixture. The reaction mixture was heated at 50° C. in an oil bath for 16 h. It was cooled to RT, diluted with EtOAc (1 L) and filtered through a pad of celite. The filtrate was concentrated in-vacuo. The organic residue was diluted with CHCl3 (400 mL) and washed with sat. aq. NaHCO3 (300 mL). The aq. layer was extracted with CHCl3 (2×300 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated in-vacuo. The crude material was purified by chromatography through two Interchim puriFlash UP (25 micron) pre-packed silica-gel column (300 gram), eluting with a gradient of 0-18% EtOAc in hexane. The mixed fractions were combined and purified by chromatography through an Interchim puriFlash UP (15 micron) pre-packed silica-gel column (120 grams), eluting with a gradient of 0-18% EtOAc in hexane. The fractions with desired material were combined and concentrated in-vacuo, to provide a mixture of (R)-methyl 4-((tert-butoxycarbonyl)amino)-3-oxopentanoate and (R,Z)-methyl 4-((tert-butoxycarbonyl)amino)-3-hydroxypent-2-enoate (21.03 g, 86 mmol, 81% yield) as white solid. ee % was not determined. m/z (ESI, +ve) 268.0 (M+23)′.

Provenance & Evidence