Dimethylformamide → N-(tert-butoxycarbonyl)-2-hydroxymethyl-4,5-dihydropyrrole

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A solution of n-butyllithium in hexanes (2.43 M, 27.6 mL, 67.0 mmol, 1.10 equiv) was added dropwise via syringe to a stirred solution of N-(tert-butoxycarbonyl)-2,3-dihydropyrrole (Oliveira et al. J. Org. Chem. 1999, 64, 6646; incorporated herein by reference) (10.3 g, 60.9 mmol, 1 equiv) in tetrahydrofuran (300 mL) at −20° C. The reaction mixture was stirred at −20° C. for 3 h, then was cooled to −78° C. The cold solution was then transferred via cannula over 25 min to a separate flask containing a stirred solution of N,N-dimethylformamide (DMF, 7.10 mL, 91.4 mmol, 1.5 equiv) in tetrahydrofuran (30 mL) at −78° C. The reaction mixture was stirred at −78° C. for 30 min, then was transferred rapidly via cannula to a vigorously stirred solution of saturated aqueous ammonium chloride (500 mL) at 23° C. Upon completion of the addition the layers that formed were separated. The aqueous layer was then extracted with two 750-mL portions of ethyl acetate. The combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate solution (300 mL) and saturated aqueous sodium chloride solution (300 mL). The washed solution was dried over sodium sulfate and the solids were filtered. The filtrate was concentrated. The residue obtained was dissolved in methanol (300 mL, 1-L round-bottom flask containing a Teflon-coated stir bar). The resulting solution was cooled to 0° C. and sodium borohydride (2.53 g, 67.0 mmol, 1.1 equiv) was added in one portion (gas evolution was observed). The mixture was stirred for 35 min at 0° C. The product solution was then slowly poured into a solution of saturated aqueous ammonium chloride (200 mL), and the biphasic mixture was diluted with water (50 mL). The layers were separated and the aqueous layer was extracted with two 500-mL portions of ethyl acetate. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution (120 mL) and hexanes (500 mL) was added. The product solution was washed with saturated aqueous sodium chloride solution (200 mL) and the washed solution was dried over sodium sulfate. The dried solution was filtered and the filtrate was concentrated. The residue obtained was purified by flash-column chromatography (20% ethyl acetate-hexanes initially, grading to 30% ethyl acetate-hexanes) to furnish N-(tert-butoxycarbonyl)-2-hydroxymethyl-4,5-dihydropyrrole as a pale yellow oil (6.75 g, 59%).

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