Sulfuric Acid → {rel-(3R,4S)-4-[(S)-1-(2,4-dimethoxy-benzylamino)-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ylsulfanyl}-acetonitrile

Participants

Reaction Conditions

Reaction Steps

2-Mercaptoacetonitrile (1.03 g, 14.1 mmol) was added dropwise to a solution of (3aS,7S,7aS)-rel-6-(2,4-dimethoxy-benzyl)-7-(2-fluoro-phenyl)-7-methyl-hexahydro-2,4-dioxa-5-thia-6-aza-indene 5,5-dioxide (4.1 g, 9.37 mmol) and 1,1,3,3-tetramethylguanidine (1.62 g, 14.1 mmol) in N,N-dimethylformamide (55 ml) at room temperature. The reaction mixture was then stirred at 60° C. for 12 hours. For the workup, the solvent was evaporated at reduced pressure, and the residue was dissolved in dichloromethane (50 ml). After addition of sulfuric acid (20%; 50 ml, 185 mmol) and stirring overnight, the mixture was poured onto a saturated solution of sodium hydrogencarbonate followed by the extraction (2×) with dichloromethane. The combined organic layers were dried over sodium sulphate and evaporated. The residue was purified by flash chromatography on silica gel using a gradient of heptane and ethyl acetate=100:0 to 0:100 as the eluent. The {rel-(3R,4S)-4-[(S)-1-(2,4-dimethoxy-benzylamino)-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ylsulfanyl}-acetonitrile (3.92 g, 97% yield) was obtained as a light brown oil. MS (ISP): m/z=431.2 [M+H]+.

Provenance & Evidence