Dimethylformamide → HCID 178451155, compound

Participants

Reaction Steps

To a vented and cooled solution (0° C.) under nitrogen of trans-4-(butoxycarbonyl)cyclohexanecarboxylic acid (J. Chem. Soc., Perkin Trans. 1, 1999, 20, 3023) (18.9 g, 83 mmol) in CH2Cl2 (150 mL) was added a catalytic amount of DMF (30 μL) followed by oxalyl chloride (7.97 mL, 91 mmol). The reaction mixture was then allowed to slowly warm to room temperature where it was stirred for 14 h at which point it was concentrated to a yellow oil and dried under vacuum for 3 h. The residue consisting primarily of butyl trans-4-(chlorocarbonyl)cyclohexanecarboxylate was diluted with THF (200 mL) and cooled in an ice bath. To this solution was added PdCl2(dppf)-CH2Cl2 (3.38 g, 4.14 mmol) followed by dimethyl zinc (2 M in PhCH3, 29 mL, 58 mmol) at such a rate that the internal temperature did not exceed 15° C. The cooling bath was then removed and after 2 h of stirring at room temperature the reaction mixture was re-cooled to 0° C. where it was diluted carefully with H2O. After the initial exotherm had subsided, sufficient 1N HCl and EtOAc were introduced such that a homogenous biphasic mixture formed. The layers were separated, the organic washed a second time with H2O then dried with MgSO4, filtered and concentrated in vacuo. The crude residue was absorbed on silica and purified by flash chromatography to afford butyl trans-4-acetylcyclohexanecarboxylate as a non-viscous orange oil. MS ESI calc'd. for C13H23O3 [M+H]+ 227. found 227. 1H NMR (500 MHz, CDCl3) δ 4.06 (t, J=6.6 Hz, 2H), 2.37-2.29 (m, 1H), 2.28-2.20 (m, 1H), 2.14 (s, 3H), 2.11-2.02 (m, 2H), 1.99 (d, J=13.8 Hz, 2H), 1.66-1.55 (m, 2H), 1.51-1.40 (m, 2H), 1.39-1.29 (m, 4H), 0.93 (t, J=7.4 Hz, 3H).

Provenance & Evidence