Sulfuric Acid → [N(E),S(R)]-N-[1-(5-Bromo-2-fluorophenyl)ethylidene]-2-methyl-2-propanesulfinamide

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Reaction Conditions

Reaction Steps

Commercially available 1-(5-bromo-2-fluorophenyl)ethanone (140 g, 645 mmol, Eq: 1.0) [CAS No. 477-89-3], (R)-2-methylpropane-2-sulfinamide (78.2, 645 mmol, Eq: 1.0) and titanium(IV) ethoxide (221 g, 204 ml, 968 mmol, Eq: 1.5) were dissolved in tetrahydrofuran (1.19 l) and the mixture heated to 75° C. and stirred at this temperature overnight. The mixture was cooled to 50° C., sat. potassium sodium tartrate solution (1.17 l, 2.58 mol, Eq: 4) was added and the mixture stirred at this temperature for 1.5 hours. The mixture was diluted with TBME, the layers separated, the organic layer washed with sulfuric acid (0.05 M, 2.36 l, 118 mmol, Eq: 0.183), sat. Na2CO3-solution (645 ml, 645 mmol, Eq: 1.00) and brine, dried over Na2SO4 and the solvent evaporated leaving an dark orange solid, which was purified by trituration with n-heptane to give the first batch (144.7 g) as an off-white solid. From the mother liquor another batch (23.0 g) was obtained by trituration with pentane, yet another batch was obtained by silica gel column chromatography with n-heptane/ethyl acetate. Total yield of (R,E)-N-(1-(5-bromo-2-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide (180.7 g, 564 mmol, 87.5% yield) as an off-white solid. MS (ISP): m/z=320.3 [M+H]+ and 322.0 [M+2+H]+.

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