N,N,N',N'-Tetramethylethylenediamine → HCID 21878154, compound

Participants

Reaction Conditions

Reaction Steps

A stirred solution of isobutyl 3,5-difluorophenylcarbamate (Step A, 10.0 g, 43.6 mmol) and N,N,N′,N′-tetramethylethylenediamine (13.7 mL, 87.3 mmol) in anhydrous THF (87 mL) at −78° C. under N2 is treated n-butyllithium (1.6M in hexanes, 35.8 mL, 89.4 mmol) dropwise over 35 mins. The mixture is stirred at −78° C. for 20 mins and is then treated with a solution of tetrahydro-2H-thiopyran-4-one (5.32 g, 45.8 mmol) in anhydrous THF (15 mL) dropwise over 10 mins. After 45 mins at −78° C., the cooling bath is removed and the mixture is allowed to warm to ambient temperature and is then quenched by the slow addition of saturated aqueous ammonium chloride (50 mL). Water (50 mL) and EtOAc (100 mL) are added, the layers are separated, and the organic phase is washed with water (100 mL) and saline (50 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product is triturated and filtered from EtOAc (approx. 25 mL) to remove an insoluble impurity, and the filtrate is chromatographed on two Flash 40M 90 g silica gel cartridges, eluting with EtOAc/heptane (20/80). Pooling and concentration of those fractions with an Rf=0.26 by TLC (EtOAc/hexanes, 25/75) gives the title compound, mp 103-104° C.

Provenance & Evidence