Bromide ion → HCID 131733518, compound

Participants

Reaction Steps

Step 1 To a solution of (S)-2-methyl-propane-2-sulfinic acid 1-(4-chloro-2-fluoro-phenyl)-meth-(E)-ylideneamide (26.2 g, 0.1 mol, 1.0 eq) in anhydrous THF (700 ml) at −75° C. was added 0.5M cyclopropylmagensium bromide in THF (400 ml, 0.2 mol, 2.0 eq) dropwise at <−65° C. over 30 min. The reaction was stirred for 2 hours at <−65° C. then allowed to warm to room temperature and stirred for 4 hours. Saturated ammonium chloride solution (300 ml), was added, followed by water (150 ml). The layers were separated and the aqueous extracted with EtOAc (3×200 ml). The combined organic layers were washed with sat. brine (300 ml), dried (MgSO4), filtered and concentrated in vacuo. The crude material was purified by column chromatography on silica (500 g), eluting with 10% EtOAc/heptanesup to 80% EtOAc. (S)-2-Methyl-propane-2-sulfinic acid [(R)-(4-chloro-2-fluoro-phenyl)cyclopropyl-methyl]-amide was isolated in two batches (combined yield 26.4 g, 86.9 mmol, 87%): 1st batch; 18.4 g 1H NMR 4:1 mixture of diastereomers in favour of desired isomer, 2nd batch; 8 g 1H NMR 19:1 mixture of diastereomers in favour of desired isomer. The 2nd batch was repurified by column chromatography on silica (500 g), eluting with 10% EtOAc/heptanesup to 80% EtOAc, to give 6.6 g of pure (S)-2-methyl-propane-2-sulfinic acid [(R)-(4-chloro-2-fluoro-phenyl)-cyclopropyl-methyl]-amide. 1H NMR (270 MHz, CDCl3): 7.33 (1H, t), 7.11 (1H, dd), 7.08 (1H, dd), 3.86 (1H, dd), 3.56 (1H, d), 1.28-1.22 (1H, m), 1.18 (9H, s), 0.90-0.80 (1H, m), 0.74-0.64 (1H, m), 0.56-0.35 (2H, m).

Provenance & Evidence