Formaldehyde → HCID 67998522, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (249 μL, 1.75 mmol) in THF (1.2 mL) was added 1.6 M n-BuLi in hexanes (984 μL, 1.57 mmol) slowly at −15° C. After 30 minutes, a solution of methyl 2-((3R,5R,6S)-1-((S)-2-(tert-butyldiphenylsilyloxy)-1-cyclopropylethyl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetate (255 mg, 0.35 mmol; Example 263, Step B) in THF (1.2 mL) was added dropwise to the LDA solution and the resulting solution was stirred at −15° C. for 30 min (the solution turned bright yellow). Then, formaldehyde in N2 stream was carried over the reaction surface for 5 min (formaldehyde was generated by cracking para-formaldehyde (105 mg, 3.50 mmol) with heat gun) at −15° C. After being stirred at −15° C. for 30 min, the reaction was allowed to warm to rt and stirred for 4 h. The reaction was quenched (ice cold sat. NH4Cl), extracted (2×EtOAc) and washed (brine×3). The combined organic layers were dried (Na2SO4) and concentrated under the reduced pressure. Purification of the residue by chromatography on silica gel (24 g SiO2, 20% and 50% EtOAc/Hex) provided the title compound as a colorless film.

Provenance & Evidence