Dimethyl Sulfoxide → (2S,3RS)-2-(4-Bromophenoxy)-5-pyridin-3-ylpent-4-yn-3-ol

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Reaction Steps

Oxalyl chloride (4.38 ml) was added dropwise to a solution of dimethylsulfoxide (4.4 ml) in dry dichloromethane (250 ml) at -60° C. The resulting solution was stirred for 20 minutes and then a solution of (2S)-2-(4-bromophenoxy)-1-propanol (9.24 g, Example 15b) in dry dichloromethane (75 ml) was added dropwise. The mixture was stirred for a further 30 minutes and then triethylamine (22.4 ml) was added dropwise. The mixture was allowed to reach room temperature with stirring over 1 hour. The mixture was diluted with anhydrous ether (100 ml), filtered and concentrated under reduced pressure. The residue was dissolved in dry tetrahydrofuran (20 ml) and added to a solution of 1-lithio-2-(pyridin-3-yl)acetylene [generated by the addition of n-butyllithium (2.5 M in hexanes, 24 ml) to a solution of (pyridin-3-yl)acetylene (6.3 g) (J. Amer. Chem. Soc. 1935, 57, 1284) in tetrahydrofuran (40 ml) at -60° C. with stirring for 20 minutes]. The mixture was stirred for 1 hour at -60° C. and was then allowed to warm to room temperature over 2 hours. The mixture was poured into saturated ammonium chloride solution (100 ml) and extracted with ethyl acetate (3×100 ml). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica eluting with ethyl acetate:hexane (1:4) and then ethyl acetate to give the sub-title compound as an oil and as a 4:1 mixture of diastereomers (8.31 g).

Provenance & Evidence