Sodium hydride → (2S,4S)-1-(Benzyloxycarbonyl)-4-(2,2-difluoroethoxy)pyrrolidine-2-carboxylic acid

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Reaction Steps

To a solution of (2S,4S)-1-(benzyloxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (5.0 g, 18.85 mmol) in THF (100 mL) was added NaH (1.583 g, 39.6 mmol) at 0° C. under N2. The resulting suspension was stirred at RT for 30 min. A solution of 1,1-difluoro-2-(trifluoromethylsulfonyl)ethane (4.11 g, 20.73 mmol) in THF (5 ml) was added to the suspension. The reaction mixture was stirred at RT for 3 h. The reaction mixture was quenched with water and concentrated. The residue was extracted with EtOAc; the aqueous layers was acidified to ph 3 with 1N HCl and extracted with EtOAc. The organic layers were washed with water and brine, dried over Na2SO4, and filtered. The crude product was used in the next step without purification. LC/MS [M−H]+: 328; Ret time (Method F): 0.93 min (Phenomenex-Luna s10 4.6×50 mm column, 4 min gradient, 4 mL/min).

Provenance & Evidence