Acetic Acid → (1S,2R,4S)-ethyl 4-(dibenzylamino)-2-methylcyclopentanecarboxylate

Participants

Reaction Conditions

Reaction Steps

A round bottom flask was charged with ethyl 2-methyl-4-oxocyclopentanecarboxylate (10.0 g, 58.8 mmol) and DCE (180 mL). The solution was cooled to about 0° C. and AcOH (5.7 mL, 100 mmol) and dibenzylamine (11.3 mL, 58.8 mmol) were added dropwise, resulting in formation of a thick suspension. The reaction mixture was warmed to about 10° C. and sodium triacetoxyborohydride (21.2 g, 100 mmol) was added portionwise. The reaction mixture was stirred at ambient temperature for about 20 h then slowly poured into stirred saturated aqueous NaHCO3 (300 mL) and stirred for about 20 min. The layers were separated and the aqueous phase was extracted with DCM (3×100 mL). The combined organic extracts were washed with brine (2×100 mL), dried over anhydrous Na2SO4, and concd under reduced pressure. The crude yellow oil was purified via silica gel chromatography eluting with a gradient of 0-30% EtOAc in heptane to give ethyl 4-(dibenzylamino)-2-methylcyclopentanecarboxylate (scalemic mixture of diastereomers), predominantly (1S,2R,4S) ethyl 4-(dibenzylamino)-2-methylcyclopentanecarboxylate (15.5 g, 75%) as a colorless oil: 1H NMR (pyridine-d5) δ 7.53 (dd, J=0.9, 7.9 Hz, 4H), 7.43-7.35 (m, 4H), 7.33-7.25 (m, 2H), 4.22-4.06 (m, 2H), 3.79 (d, J=14.2 Hz, 2H), 3.70 (d, J=14.2 Hz, 2H), 3.34-3.22 (m, 1H), 2.76 (dd, J=7.9, 16.6 Hz, 1H), 2.25-2.13 (m, 1H), 2.09-1.94 (m, 2H), 1.88-1.79 (m, 1H), 1.52 (dd, J=10.5, 22.5 Hz, 1H), 1.16 (t, J=7.1 Hz, 3H), 0.98 (d, J=7.0 Hz, 3H).

Provenance & Evidence