Diisopropylamine → Methyl 2,2-dimethyl-3-(4-nitrophenyl)propanoate

Participants

Reaction Conditions

Reaction Steps

n-BuLi (1.15M in hexane) (10.1 mL, 11.6 mmol) was added dropwise to a solution of diisopropylamine (1.64 mL, 11.6 mmol) in THF (20 mL) in a dry ice/acetone bath. The mixture was stirred and warmed to ˜−50° C. before being cooled again and methyl 2-methylpropanoate (1.3 mL, 11 mmol) was added over 5 min. The mixture was stirred for 30 min before a solution of the nitrobenzyl bromide (2 g in 15 mL THF) was added dropwise over 20 min. The temperature was kept below −65° C. during the addition then left in the cool bath to warm slowly to RT and stirred for 16 hr. The mixture was quenched with NH4Cl (sat.) and left at RT for 9 days. The quenched reaction mixture was diluted with water and EtOAc and extracted into EtOAc (3×40 mL). The organics were combined, dried with brine, then solid MgSO4, filtered and the solvent removed to afford a crude oil. The oil was dissolved in ˜2 mL DCM and applied to a silica column to afford (i) 1.4 g (64%). 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J=8.8 Hz, 2H), 7.27 (d, J=9.6 Hz, 2H), 3.67 (s, 3H), 2.96 (s, 2H), 1.21 (s, 6H).

Provenance & Evidence