HCID 58057079, Verbindung → (R)-3-((E)-2-(pyrrolidin-3-yl)vinyl)-5-(tetrahydro-2H-pyran-4-yloxy)pyridine

Beteiligte Stoffe

Reaktionsschritte

A solution of tert-butyl (R)-(E)-3-(2-(5-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-yl)vinyl)pyrrolidine-1-carboxylate (18 g, 48.13 mmol) in dichloromethane (40 mL) and trifluoroacetic acid (40 mL) was stirred at ambient temperature for 2 h. The reaction was concentrated on a rotary evaporator, and the residue was partitioned between saturated sodium chloride (50 mL) and chloroform (100 mL). The mixture was basified to pH 9 with 10% aqueous sodium hydroxide solution. The organic layer was separated and the aqueous layer extracted with chloroform (2×100 mL). The combined organic layers were dried over sodium sulfate and concentrated on a rotary evaporator to give (R)-3-((E)-2-(pyrrolidin-3-yl)vinyl)-5-(tetrahydro-2H-pyran-4-yloxy)pyridine (8.0 g) as a gum. This was dissolved in methanol (100 mL) and galactaric acid (3.0 g, 14.6 mmol) was added and the mixture was heated to reflux. This hot solution was filtered, and filtrate was allowed to cool to ambient temperature. The crystallized product was filtered and solid was suspended in 10% water in ethanol (180 mL). The suspension was heated to reflux and hot solution was filtered. The filtrate was allowed to cool to ambient temperature. Crystallized product was filtered and dried on high vacuum pump to give (R)-3-((E)-2-pyrrolidin-3-ylvinyl)-5-(tetrahydro-2H-pyran-4-yloxy)pyridine hemigalactarate (4.5 g). MP: 179° C. 1H-NMR (CD3OD, 300 MHz): δ 8.04 (s, 1 H), 8.01 (d, J=2.2 Hz, 1 H), 7.36 (s, 1 H), 6.46 (d, J=16.0 Hz, 1 H), 6.21 (dd, J=16.0, 7.5 Hz, 1 H), 4.65-4.4.54 (m, 1 H), 4.12 (s, 1 H), 3.89-3.83 (m, 2 H), 4.80 (s, 1 H), 3.56-3.33 (m, 4 H), 3.27-3.18 (m, 1 H), 3.12-2.96 (m, 2 H), 2.23-2.14 (m, 1 H), 1.98-1.91 (m, 2 H), 1.88-1.78 (m, 1 H), 1.68-1.58 (m, 2 H); MS (m/z): 275 (M+1).

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