Diethyl Ether → HCID 117892466, compound

Participants

Reaction Steps

Step 1 To a solution of (R)-(+)-2-methyl-propane-2-sulfinic acid 1-(4-chloro-2-fluoro-phenyl)-meth-(E)-ylideneamide (50 g, 0.191 mol, 1.0 eq) in THF (1 L) at −75° C. was added 3M ethylmagnesium bromide in Et2O (127.4 ml, 0.382 mol, 2.0 eq) slowly at <−65° C. over 30 min. The reaction was stirred for 2.5 h at <−65° C. before addition of sat. ammonium chloride solution (500 ml). The solution was diluted with water (250 ml) and the organic layer separated. The aqueous layer was extracted with EtOAc (2×500 ml) and the combined organic layers were washed with brine (500 ml), dried over MgSO4, filtered and concentrated in vacuo to afford 59 g of crude material (3:1 mixture of diastereomers by 1H NMR). The crude material was purified by chromatography (silica, 1 Kg) eluting with 20% EtOAc/heptanes up to 30% EtOAc to give (R)-(+)-2-methyl-propane-2-sulfinic acid [(R)-1-(4-chloro-2-fluoro-phenyl)-propyl]-amide (19.9 g, 1H NMR>95%, 0.0682 mol, 34% yield). 1H NMR (270 MHz, CDCl3): 7.27-7.21 (1H, m), 7.13-7.04 (2H, m), 4.43 (1H, q), 3.50 (1H, d), 2.02-1.72 (2H, m), 1.21 (9H, s), 0.89 (3H, t).

Provenance & Evidence