Sulfuric Acid → Ethyl-5-(4-[2-fluorobenzyloxy]phenyl)-3,4-dihydro-2H-pyrrole-2-carboxyate

Participants

Reaction Conditions

Reaction Steps

(S)-4-Isopropyl-2-[(S)-2-(diphenylphosphino)ferrocen-1-yl]oxazoline (18.8 mg, 0.039 mmol) and Cu(MeCN)4PF6 (14.5 mg, 0.039 mmol) were added to a dried, nitrogen swept reaction vessel. Anhydrous, degassed, BHT inhibited THF (5.0 mL) was then added and the mixture was stirred for 30 minutes at 20-25° C. The resulting solution was then cooled to −78° C. and a solution of 1-(4-[2-fluorobenzyloxy]phenyl)-2-propen-1-one (P4, 2.0 g, 7.80 mmol) and ethyl N-(diphenylmethylidene)glycinate (2.29 g, 8.58 mmol) in THF (15 mL total volume) was added over 1-2 minutes. After 3-5 minutes, a solution of DBU (5.9 mg, 0.039 mmol) in THF (0.5 mL total volume) was added. The solution was then stirred for 8-12 hours at −78° C. The reaction mixture was then warmed to 0-5° C. and 1 M H2SO4 (aq., 25 mL) was then added. The reaction mixture was then warmed to 20-25° C. and mixed vigorously for 2 hours. The mixture was then poured into a rapidly stirring solution of NaHCO3 (saturated, enough to bring the pH to 7.0). After 5 minutes of stirring, the mixture was extracted twice with TBME and the organic extracts were pooled, dried over Na2SO4, and concentrated to near dryness. The resulting residue was purified by flash column chromatography eluting with 0→40% acetone/hexanes (gradient). Concentration of the fractions containing the title compound gave a crystalline solid (2.23 g, 84% yield).

Provenance & Evidence