Diiodomethane → Lithium diisopropylamide

Participants

Reaction Steps

Lithium diisopropylamide was prepared by the addition of 2.5M N-butyl lithium (5.6 mL, 13.9 mmol) in hexanes to a solution of diisopropylamine (1.95 mL, 13.9 mmmol) in tetrahydrofuran (30 mL) at 0° C. with stirring for 20 minutes. Then a solution of tetrahydropyran-4-carboxylic acid ethyl ester (2 g, 12.7 mmol) in tetrahydrofuran (8 mL) was added to the solution of lithium diisopropylamide at a temperature of -78° C. over 15 minutes. The resulting solution was stirred an additional 50 minutes, and diiodomethane (1.14 mL, 14.2 mmol) was added. The resulting mixture was stirred an additional 50 minutes, warmed to room temperature over 30 minutes, then recooled to 0° C. The mixture was diluted with 1M aqueous hydrochloric acid (25 ml), extracted with diethyl ether (2×100 mL), and washed with additional portions of diethyl ether (2×50 mL). The combined organic layers were washed once with 1M aqueous hydrochloric acid (100 mL), saturated aqueous sodium bisulfite (100 mL), saturated aqueous sodium bicarbonate (100 mL), and dried over magnesium sulfate, and concentrated in vacuo. The residue was filtered over a plug of silica gel, eluting successively with hexanes and ethyl acetate, removing excess alkylating agent with the hexane wash, to afford pure 4-(iodomethyl)tetrahydropyran-4-carboxylic acid ethyl ester as a pale yellow oil which was taken directly into the next reaction without further purification (3.20 g, 85%). IR (KBr) 1732 cm-1 ; 1HNMR (CDCl3) 1.31 (q, J=7.3 Hz, 3H), 1.56 (ddd, J=14.6, 10.9, 4.5, 2H), 2.17 (ddd, J=14.6, 5.7, 3.3, 2H), 3.31 (s, 2H), 3.51 (ddd, J=11.7, 11.1, 2.5 Hz, 2H), 3.51 (td, J=11.7, 4.3 Hz, 2H), 4.24 (q, J=7.1 Hz, 2H); 13CNMR (CDCl3) δ 14.33 (q) , 15.04 (t), 34.70 (t), 45.26 (s), 61.34 (t), 65.22 (t), 172.89 (s); EIHRMS Calcd. for C9H15IO3 (M+): 298.0066. Found: 298.0066. Anal. Calcd. for C9H15IO3 : C, 36.26; H, 5.07. Found: C, 36.56; H, 5.09.

Provenance & Evidence