2-Chloro-1-(6-(2,5-dimethyl-1H-pyrrol-1-YL)pyridin-3-YL)ethanone → (1R)-2-Chloro-1-[6-(2.5-dimethyl-pyrrol-1-yl)-pyridin-3-yl]-ethanol
Reaction equation
B1([C@H]2[C@H](C)[C@@H]3C(C)(C)[C@H](C3)C2)C2CCCC1CCC2.[Cl:20][CH2:21][C:22]([C:24]1[CH:25]=[N:26][C:27]([N:30]2[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]2[CH3:36])=[CH:28][CH:29]=1)=[O:23]>>[Cl:20][CH2:21][C@@H:22]([C:24]1[CH:25]=[N:26][C:27]([N:30]2[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]2[CH3:36])=[CH:28][CH:29]=1)[OH:23]Participants
3
Conditions
- Temperature
- 0 °C
Procedure
(R)-Alpine borane (1.5 L, 0.5 M in tetrahydrofuran) was added slowly to a cooled (0° C.), neat, 2-chloro-1-[6-(2,5-dimethyl-pyrrol-1-yl)-pyridin-3-yl]-ethanone (Example 140; 93 g). The mixture was warmed to room temperature and reduced to one third its original volume by distilling tetrahydrofuran. After four days, the mixture was cooled to 0° C. and 3 M aqueous solution of K2CO3 (600 mL) was added. Then the reaction mixture was oxidized by drop wise addition of 30% H2O2 (250 mL). After stirring at room temperature for 3 h, the reaction mixture was diluted ethyl acetate, organic layer was separated. Aqueous portion was extracted (ethyl acetate), combined organic extracts were washed with water and dried. After concentration in vacuo, the resulting oil was purified by chromatography on silica gel (hexanes/ethyl acetate as eluent) to afford a yellow solid (35 g). 1H NMR (CDCl3, 300 MHz) δ 8.59 (m, 1 H), 7.88 (dd, 8.1 Hz, 2.2 Hz, 1 H), 7.26 (m, 1 H), 5.91 (m, 2 H), 4.96 (m, 1 H), 3.78 (m, 2 H), 3.35 (br s, 1 H), 2.11 (2, 6 H); MS (FAB) m/z 251 (MH+); Anal. calcd for C13H15N2OCl: C, 62.28; H, 6.03; N, 11.17. Found: C, 61.95; H, 6.03; N, 10.92; Rf =0.4 (60:40 hexanes/ethyl acetate).