Tetramethyltin → (R,R)-N-[3-(3-fluoro-4-methoxyphenyl)-4-methylisothiazol-5-yl]-2-methylcyclopropanecarboxamide

Participants

Reaction Conditions

Reaction Steps

Add PdCl2(PPh3)2 (0.15 g, 0.21 mmol) and Sn(CH3)4 (0.79 mL, 1.02 g, 5.71 mmol) to (R,R)—N-[4-bromo-3-(3-fluoro-4-methoxyphenyl)-isothiazol-5-yl]-2-methylcyclopropanecarboxamide (0.55 g, 1.43 mmol) in DMF (3 mL), and stir the reaction mixture at 130° C. in a sealed tube overnight. Dilute with EtOAc (100 mL) and brine (100 mL). Collect the organic phase, dry (K2CO3) and evaporate. Take up the resultant oil in 1:1 MTBE:KF (aqueous, 15%) (50 mL) and stir at reflux for 1 h. Pour the cooled solution over diatomaceous earth and filter with MTBE (100 mL). Collect the organic phase, dry (K2CO3) and evaporate. Chromatography over silica gel, eluting with 10-30% THF in hexane, affords (R,R)—N-[3-(3-fluoro-4-methoxyphenyl)-4-methylisothiazol-5-yl]-2-methylcyclopropanecarboxamide. Yield: 49.2%. ES-MS: m/e 321.0 (m+1).

Provenance & Evidence