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

Temperatur

0 °C

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.

1. temperaturecooled to −78° C
2. stirringthe reaction was stirred 15 minutes at −78° C
3. customThe bath was removed
4. temperatureto warm to room temperature
5. stirringAfter stirring an additional 5 hours
6. customthe reaction mixture was quenched with saturated NH4Cl solution
7. customthe organics were removed in vacuo
8. extractionThe oily mixture was extracted with ethyl acetate
9. dry with materialThe organic was dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe crude oil was purified by on silica gel (25:1 hexanes:EtOAc)

ORD-Eintrag

ord-139b934eba2f4865929f0ebf371aae63

Quelldatensatz

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08680114B2