Hydrochloric Acid → Diethyl propylmalonate

Temperature

23 °C

To a suspension of sodium hydride (60% dispersion in mineral oil, 12.6 g, 315 mmol, 1.05 equiv) in DMF (300 mL) at 23° C. was added a solution of diethyl malonate (45.5 mL, 300 mmol, 1 equiv) in DMF (100 mL) via cannula over the course of 10 min. The addition caused a mild exotherm and H2 gas evolution was observed, cooling was not necessary. Following the addition, the reaction was stirred for 45 min at 23° C. then treated with 1-bromopropane (27.3 mL, 300 mmol, 1 equiv). The reaction was stirred at 23° C. for 25 min, then heated to 65° C. for 3 h, then stirred at 23° C. overnight. The reaction mixture was added to 1.0 N HCl (1 L) then extracted with diethyl ether (700 mL). The ether extracts were washed with H2O (400 mL), brine (200 mL), dried (MgSO4), filtered and concentrated to give 65.1 g of product as a clear oil. 13C NMR revealed approximately 4:1 mono to bis-alkylated product ratio. The product diethyl n-propylmalonate was used without further purification: 1H NMR (300 MHz, CDCl3) 4.18 (q, J=6.9 Hz, 4H), 3.32 (t, J=7.8 Hz, 1H), 1.91-1.79 (m, 2H), 1.41-1.25 (m, 2H), 1.25 (t, J=6.9 Hz, 6H), 0.92 (t, J=7.5 Hz, 3H); 13C NMR (300 MHz, CDCl3) (*denotes signal due to minor product of bis-alkylation) 169.6, 61.2, 60.9*, 51.8, 34.4*, 30.7, 20.5, 17.3*, 14.4*, 14.0, 13.7.

1. additionThe addition
2. temperaturecooling
3. additionthe addition
4. stirringThe reaction was stirred at 23° C. for 25 min
5. temperatureheated to 65° C. for 3 h
6. stirringstirred at 23° C. overnight
7. extractionthen extracted with diethyl ether (700 mL)
8. washThe ether extracts were washed with H2O (400 mL), brine (200 mL)
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-0f411fd022cc40f297ba0d2988647c13

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07256177B2