1,4-Dibromobutane → 1-Pyrrolidineethanol,beta-methyl-,(betaS)-(9CI)

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Reaction Steps

Potassium carbonate (41.4 g, 0.30 moles) was added to a solution of (S)-(+)-2-amino-1-propanol (11.27 g, 0.15 moles, Aldrich) in anhydrous acetonitrile (1.5 L) then 1,4-dibromobutane (17.9 mL, 0.15 moles, Aldrich) was added. The resulting mixture was refluxed for 24 hours then cooled to room temperature and filtered. The filtrate was concentrated under vacuum to a straw-colored solid which was dissolved in dichloromethane (150 mL) and again concentrated under vacuum to afford a straw-colored solid. This crude material, believed to be a mixture of the hydrobromide salt and the free base of the product, was again dissolved in dichloromethane (200 mL). Solid potassium carbonate and the mixture was stirred vigorously for 3 hours then filtered and concentrated under vacuum to afford a straw-colored solid. This solid, believed to still be partially the hydrobromide salt, was partitioned between dichloromethane (150 mL) and saturated aqueous potassium carbonate (50 mL). The layers (upper layer organic, lower layer aqueous) were separated and the aqueous layer was extracted with dichloromethane (2×100 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated to an amber oil. This crude product was purified by short-path vacuum distillation to afford the title compound as a colorless liquid (bp 53–54.5° C. at 1.5 mm Hg). NMR: (CDCl3, 600 MHz) δ 3.59 & 3.36 (2H, 2 dd, J=4, 10 Hz, H1), 2.64–2.72 (1H, m, H2), 2.54–2.62 (4H, m, H2′ & H5′), 1.72–1.80 (4H, m, H3′ & H4′),1.04 (3H, d, J=7 Hz, H3); MS (electrospray): m/e 130 (M+H), 112 (M−OH). [α]D+0.9°

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