Triphenylphosphine → (5R,6S,9R)-5-chloro-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine

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Reaction Steps

In an oven-dried 250 mL round-bottom flask was suspended NCS (0.751 g, 5.62 mmol) in tetrahydrofuran (15 mL). Triphenylphosphine (1.475 g, 5.62 mmol) was added. After stirring under nitrogen for 5 min, (5S,6S,9R)-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-ol (1.007 g, 2.250 mmol) was added in one portion to the gray suspension. The resulting reddish suspension was stirred at room temperature. The solids gradually dissolved to give a tan solution. After 5 h, LCMS indicated complete conversion. Tetrahydrofuran was removed in vacuo and the remaining red oil was directly purified by ISCO (240 g silica column) up to 60% ethyl acetate/hexane. Pure ethyl acetate eluted the non polar component and the product was eluted by 10% methanol (with 2.0M NH4OH) in methylene chloride. The product fractions were combined and re-purified by FCC up to 50% ethyl acetate/hexane to afford the desired product as a colorless oil (869 mg, 83%). MS (ESI) [M+H+]=466.22; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.55 (d, J=3.53 Hz, 1H) 7.63 (br. s., 1H) 7.20 (dd, J=7.68, 4.91 Hz, 1H) 7.01-7.15 (m, 1H) 6.90-7.01 (m, 1H) 6.66-6.90 (m, 1H) 5.55-5.85 (m, 1H) 5.40-5.56 (m, 1H) 3.96-4.33 (m, 1H) 2.33 (br. s., 3H) 2.09-2.20 (m, 1H) 1.14-1.23 (m, 3H) 1.04-1.14 (m, 9H) 1.01 (d, J=7.30 Hz, 9H).

Provenance & Evidence