Formaldehyde → Ethyl 4-(hydroxymethyl)oxane-4-carboxylate

Participants

Reaction Steps

Lithium diisopropylamide was prepared by the addition of 2.5M N-butyl lithium (30.3 mL, 75.6 mmol) in hexanes to a solution of diisopropylamine (10.6 mL, 75.6 mmmol) in tetrahydrofuran (244 mL) at 0° C. and stirring for 20 minutes. Then a solution of tetrahydropyran-4-carboxylic acid ethyl ester (10 g, 63.2 mmol) in tetrahydrofuran (50 mL) was added to the solution of lithium diisopropylamide over 15 minutes at -78° C. The resulting solution was stirred an additional 50 minutes, and solid paraformaldehyde (10 g) was added in one portion. The mixture was slowly allowed to warm to room temperature over 9 hours, diluted with 2M aqueous hydrochloric acid (100 mL), and filtered over a pad of celite pad which was washed with diethyl ether (2×200 mL). The aqueous layer of the filtrate was washed with additional portions of diethyl ether (2×200 mL). The combined organic layers were washed once with 2M aqueous hydrochloric acid (100 mL), saturated aqueous sodium bicarbonate (100 mL), dried over magnesium sulfate, and concentrated in vacuo to afford a slightly impure product 4-(hydroxymethyl)tetrahydropyran-4-carboxylic acid ethyl ester (11.5 g, 97%), which was taken into the next reaction without further purification. IR (neat) 3433 (br), 1726 cm-1 ; 1HNMR (CDCl3) δ 1.30 (t, J=7.1 Hz, 3H), 1.57 (ddd, J=13.8, 10.1, 4.4 Hz, 2H), 2.07 (dm, J=13.8 Hz, 2H), 2.30-2.45 (br s, 1H), 3.56 (ddd, J=11.9, 10.3, 2.7 Hz, 2H), 3.66 (s, 2H), 3.82 (dt, J=11.9, 4.2 Hz, 2H), 4.24 (q, J=7.2 Hz, 2H); 13CNMR (CDCl3) δ 14.25 (q), 30.54 (t), 46.63 (s), 61.04 (t), 64.79 (t), 69.02 (t), 175.24 (s); HRMS Calcd for C9H16O4 : 188.1049. Found: 188.1053.

Provenance & Evidence