Diisopropylamine → (RS)-2-(4,4-dimethyl-thiochroman-6-yl)-heptanoic acid

Participants

Reaction Conditions

Reaction Steps

1.12 ml of diisopropylamine were dissolved in 24 ml THF and treated dropwise, at 0° C., with 3.2 ml of butyl lithium (2.5M). After 30 min. at 0° C., a solution of 0.6 g of (4,4-dimethyl-thiochroman-6-yl)-acetic acid in 4 ml of THF was dropped in. The reaction mixture was stirred at 0° C. for one hour then at room temperature for 30 min. After cooling back to 0° C., a solution of 0.5 ml of pentyl iodide in 2 ml THF was added dropwise. The mixture was kept at 0° C. for one hour then at room temperature for two hours. The mixture was quenched with the addition of 25 ml of water and the pH was adjusted to 2 with HCl 1N. The mixture was extracted with three portions of 25 ml of ether. The combined organic extracts were washed with two portions of 25 ml of water and one portion of 25 ml of saturated aqueous sodium chloride solution. The organic phase was dried over MgSO4 and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, 10% methanol/methylene chloride), yielding 0.65 g of a pale yellow oil. 1H NMR (CDCl3): 7.27 (d, J=1.8 Hz, 1H), 7.04 (d, J=8.1 Hz, 1H), 6.99 (dd, J=8.1, 1.8 Hz, 1H), 3.46 (t, J=7.7 Hz, 1H), 3.05-2.95 (m, 2H), 2.15-1.95 (m, 3H), 1.85-1.60 (m, 1H), 1.32 (s, 3H), 1.31 (s, 3H), 1.35-1.20 (m, 6H), 0.86 (t, J=6.7 Hz, 3H).

Provenance & Evidence