Ethyl orthoformate → Ethyl 3,3-diethoxy-2-nitropropanoate

Temperature

-10 °C

Ethyl nitroacetate (1.70 ml, 15.31 mmol) was dissolved in dichloromethane (50 ml). Mixture was cooled to −10° C. Titanium(IV) chloride (1.90 ml, 17.23 mmol) was added to the mixture drop-wise. Mixture was held at −10° C. with stirring for 15 minutes. A solution of N,N-diisopropylethylamine (3.0 ml, 17.22 mmol) in 10 mL dichloromethane was added to the mixture drop-wise over 25 minutes. Mixture was held at −10° C. with stirring for 1.25 hours. Triethyl orthoformate (6.4 ml, 38.5 mmol) was added to the mixture drop-wise. Reaction was held at −10° C. with stirring for 2 hours. Reaction mixture was poured into a mixture of 40 mL ethanol and 100 mL aqueous sodium bicarbonate to quench. Mixture was stirred vigorously for 10 minutes. Organic solvents were removed from the mixture by roto-vap. Residue was treated with ethyl acetate and celite. Slurry was filtered over celite. Filtrate layers were separated. Aqueous phase was back extracted twice with ethyl acetate. Organic phases were combined. Material was dried MgSO4, filtered and then concentrated to dryness. Title compound was obtained as yellow oil in 68% yield. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 5.19-5.26 (m, 1 H) 5.10-5.17 (m, 1 H) 4.26 (q, J=6.95 Hz, 2 H) 3.68-3.85 (m, 2 H) 3.52-3.68 (m, 2 H) 1.28 (t, J=7.14 Hz, 3 H) 1.12-1.21 (m, 6 H).

1. customwas held at −10° C.
2. customwas held at −10° C.
3. stirringwith stirring for 1.25 hours
4. customReaction
5. customwas held at −10° C.
6. stirringwith stirring for 2 hours
7. customReaction mixture
8. customto quench
9. stirringMixture was stirred vigorously for 10 minutes
10. customOrganic solvents were removed from the mixture by roto-vap
11. additionResidue was treated with ethyl acetate and celite
12. filtrationSlurry was filtered over celite
13. customFiltrate layers were separated
14. extractionAqueous phase was back extracted twice with ethyl acetate
15. filtrationfiltered
16. concentrationconcentrated to dryness

ORD record

ord-e89bca4718f4484eb32decf7bb640b1f

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07470680B2