Ethyl cyanoacetate → 2-Cyano-3-(1-methyl-cyclopropyl)-acrylic acid ethyl ester

To 1-methylcyclopropane-methanol (Aldrich, 1.13 mL, 11.6 mmol) in 50 mL CH2Cl2 was added neutral alumina (2.5 g) and then PCC (2.5 g, 11.6 mmol), and the mixture stirred 3 h at ambient temperature. The mixture was filtered through a 1 cm plug of silica gel under vacuum, and rinsed with Et2O. The filtrate was concentrated to ca. 5 mL total volume. To the residue was added THF (10 mL), ethyl cyanoacetate (1.2 mL, 11.3 mmol), piperidine (5 drops), and finally acetic acid (5 drops). The whole was stirred at ambient temperature overnight, then partitioned between Et2O and sat. aq. NaHCO3. The phases were separated and the organic phase washed with brine, dried (MgSO4), and concentrated. Flash chromatography of the residue (10→15% EtOAc/hexanes) provided 0.53 g (25%) of the ester as a colorless oil that crystallized on standing, mp 35–37° C. 1H NMR (CDCl3) δ 6.99 (s, 1H), 4.27 (q, J=7.3 Hz, 2H), 1.55 (s, 3H), 1.32 (t, J=7.3 Hz, 3H), 1.14 (s, 2H), 1.07 (s, 2H). 13C NMR δ. 170.44, 162.90, 115.17, 103.69, 62.52, 21.24, 21.07 (2C), 20.71, 14.35. Anal. Calcd for C10H13NO2: C, 67.02; H, 7.31; N, 7.82. Found: C, 66.86; H, 7.47; N, 7.70.

1. filtrationThe mixture was filtered through a 1 cm plug of silica gel under vacuum
2. washrinsed with Et2O
3. concentrationThe filtrate was concentrated to ca. 5 mL total volume
4. custompartitioned between Et2O and sat. aq. NaHCO3
5. customThe phases were separated
6. washthe organic phase washed with brine
7. dry with materialdried (MgSO4)
8. concentrationconcentrated

ORD record

ord-3422341d61534d2482a7fe250de9e7ad

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07112610B2