Boron trifluoride etherate → (S)-1-tert-butyl 2-methyl 2,4,4-trimethylpyrrolidine-1,2-dicarboxylate

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Reaction Conditions

Reaction Steps

To a stirred solution of (S)-1-tert-butyl 2-methyl 2,4,4-trimethyl-5-oxopyrrolidine-1,2-dicarboxylate 106C (13.96 g, 48.9 mmol) in THF (100 mL) was added Super-hydride (lithium triethylboro-hydride) (58.7 mL, 58.7 mmol) at −78° C. under nitrogen atmosphere. The reaction mixture was stirred at −78° C. for 2 h and quenched with saturated NaHCO3 at −78° C. The reaction mixture was warmed to 0° C. and hydrogen peroxide (15 ml) was added drop-wise at 0° C. The mixture was stirred at 0° C. for 30 min and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over Na2SO4. After concentration, the crude product was used for the next step without purification. To a stirred solution of the crude product obtained above in CH2Cl2, was added half of triethylsilane (17.19 mL., 108 mmol) and half of BF3.OEt2 (13.64 mL., 108 mmol) at −78° C. under nitrogen atmosphere. The reaction mixture was stirred at −78° C. for 1 h, then the remaining triethylsilane (17.19 mL., 108 mmol) and BF3.OEt2 (13.64 mL, 108 mmol) were added. The reaction mixture was stirred at −78° C. for 2 h and quenched with saturated NaHCO3 solution. The reaction mixture was extracted with CH2Cl2. The combined organic layers were washed with water and brine, dried over Na2SO4. The crude product was purified by Biotage (0-30% EtOAc/Hexane, 1.5 L) to give (S)-1-tert-butyl 2-methyl 2,4,4-trimethylpyrrolidine-1,2-dicarboxylate 106D (10 g, 75%) as an oil.

Provenance & Evidence