Diisopropylamine → 2-p-Tolyl-succinic acid 4-tert-butyl ester 1-methyl ester

Participants

Reaction Conditions

Reaction Steps

n-BuLi (1.60M in hexanes, 40.7 mL, 65.1 mmol) was added to a 0° C. solution of diisopropylamine (9.4 mL, 67.0) in 280 mL THF. The mixture was allowed to stir at 0° C. for 30 minutes, then cooled to −78° C. A solution of p-tolyl-acetic acid methyl ester (10.48 g, 63.8 mmol; prepared from p-tolyl-acetic acid) in 10 mL of THF was added to the −78° C. LDA solution by syringe, which was then stirred for 45 minutes. Neat tert-butyl bromoacetate (28 mL) was added by syringe, and the reaction was stirred 15 minutes at −78° C. The bath was removed, and the reaction was allowed to warm to room temperature. After stirring an additional 5 hours, the reaction mixture was quenched with saturated NH4Cl solution, and the organics were removed in vacuo. The oily mixture was extracted with ethyl acetate, and the organics were combined. The organic was dried over MgSO4, filtered, and concentrated in vacuo. The crude oil was purified by on silica gel (25:1 hexanes:EtOAc) to afford the 2-p-tolyl-succinic acid 4-tert-butyl ester 1-methyl ester as a pale yellow oil (15.3 g, 86%). 1H NMR (CDCl3, 400 MHz) δ 7.16 (d, J=8.0 Hz, 2H), 7.12 (d, J=8.0 Hz, 2H), 3.99 (dd, J=10.4, 5.6 Hz, 1H), 3.66 (s, 3H), 3.09 (dd, J=16.8, 10.4 Hz, 1H), 2.57 (dd, J=16.8, 5.6 Hz, 1H), 2.32 (s, 3H), 1.41 (m, 1H). HPLC Rt=3.71 min.

Provenance & Evidence