Acetaldehyde → 4-(1-Hydroxy-ethyl)-tetrahydro-thiopyran-4-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of N,N-diisopropylamine (1.51 g, 2.1 mL, 15 mmol) in anhydrous tetrahydrofuran (10 mL) was stirred at −78° C. under nitrogen. n-Butyl lithium (6 mL, 15 mmol, 2.5 M solution in hexane) was added dropwise and the reaction mixture was stirred at −78° C. for 30 min. A solution of tetrahydro-thiopyran-4-carboxylic acid methyl ester (1.60 g, 10 mmol) in tetrahydrofuran (4 mL) was added and the reaction mixture was stirred at −78° C. for 20 min. Acetaldehyde (1.32 g, 1.7 mL, 30 mmol) was then added in one portion. The cooling bath was removed and the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was cooled to 0° C. and ice-cold hydrochloric acid (2 M) was added to acidify the reaction mixture to pH 2. Sodium chloride was added to saturate the aqueous phase and the mixture was extracted with diethyl ether. The organic extracts were combined and washed with brine. The organic solution was filtered through a hydrophobic frit and the filtrate was evaporated. The residue was purified by silica gel chromatography using a gradient of pentane/diethyl ether 3:1 to 1:3 to afford the title compound (1.77 g, 87%) as a yellow oil. 1H NMR (300 MHz, d6-DMSO): δ 0.96 (d, J=6.5 Hz, 3H), 1.46-1.73 (m, 2H), 2.12-2.28 (m, 2H), 2.43-2.57 (m, 4H), 3.50-3.58 (m, 1H), 3.63 (s, 3H), 4.85 (d, J=5.8 Hz, 1H). LCMS (m/z) 227.1 [M+Na], Tr=1.53 min.

Provenance & Evidence