二甲基 (2R)-2-羟基-2-甲基丁二酸二甲酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (R)-dimethyl 2-hydroxy-2-methylsuccinate (530 mg, 3.0 mmol) in DCM (10 mL) at 0° C. was added dropwise trichloroacetyl isocyanate (530 mL, 4.5 mmol). The ice bath was removed and the reaction mixture stirred for 2 h then quenched by the addition of MeOH (2 mL) and evaporated under reduced pressure to dryness. To the residue was added 1 M K2CO3 (15 mL, 15 mmol) and the reaction mixture heated at reflux for 0.5 h. The reaction mixture was allowed to cool to rt, extracted with Et2O (2×), then acidified to pH 2 by the addition of 1 N HCl and extracted with EtOAc (3×). The combined extracts were dried (Na2SO4) filtered and concentrated under reduced pressure. The residue was triturated with Et2O, and the triturate evaporated under reduced pressure. The residue was chromatographed by silica gel chromatography eluting with 1 to 10% MeOH/DCM (bromocresol green stain) to give Compound 42a (130 mg, 24% yield) as a clear colorless oil which solidified upon standing. 1H NMR (400 MHz, CDCl3) δ 8.95 (br. s., 1H), 3.14 (d, J=17.3 Hz, 1H), 2.97 (d, J=17.3 Hz, 1H), 1.62 (s, 3H). The structure was confirmed by single crystal X-ray diffraction analysis with material crystallized from Et2O/hexanes. The ice bath was removed then quenched by the addition of MeOH (2 mL) evaporated under reduced pressure to dryness the reaction mixture heated at reflux for 0.5 h extracted with Et2O (2×) acidified to pH 2 by the addition of 1 N HCl extracted with EtOAc (3×) The combined extracts were dried (Na2SO4) filtered concentrated under reduced pressure The residue was triturated with Et2O the triturate evaporated under reduced pressure The residue was chromatographed by silica gel chromatography eluting with 1 to 10% MeOH/DCM (bromocresol green stain)