Methyl cyanoacetate → Methyl 1-cyanocyclobutane-1-carboxylate

Temperature

-7.5 °C

To methyl cyanoacetate (10 g, 0.1 mol) under N2, N,N-dimethylformamide (DMF, 10 mL) was added at room temperature. After 10 min, the solution was added 1,8-diazabicyclo [5,4,0]undec-7-ene (DBU, 33.4 g, 0.22 mol) at 10-20° C., and then reacted 15 min at 50° C. The mixture was cooled to −5 to −10° C., 1,3-dibromopropane (20.4 g, 0.1 mol) in DMF (10 mL) added by syringe, reacted 15 min at room temperature, rose up to 70° C., and then reacted 30 min. The mixture was evaporated and the residue taken up in H2O and extracted with CHCl3 (3×50 mL). The chloroform phase was evaporated under reduced pressure. The compound 1 was purified by column chromatography (SiO2, hexane/acetone 8:1), yielding 8.74 g (62.81%). MS (ESI): m/z: 140.08 [M+H]+. Anal. Calcd (Found) for C7H9NO2: C, 60.42 (60.74); H, 6.52 (6.58); N, 10.07 (10.21). 1H NMR (D2O, 400 MHz), δ ((ppm): 3.84 (s, 3H, —OCH3), 2.73-2.63 (m, 4H, —C—CH2—CH2—CH2—), 2.17-2.32 (m, 2H, —C—CH2—CH2—CH2—). 13C NMR (D2O, 400 MHz), δ (ppm): 169.17, 128.11, 53.50, 39.38, 31.22, 17.18.

1. customreacted 15 min at 50° C
2. customreacted 15 min at room temperature
3. customrose up to 70° C.
4. customreacted 30 min
5. customThe mixture was evaporated
6. extractionextracted with CHCl3 (3×50 mL)
7. customThe chloroform phase was evaporated under reduced pressure
8. customThe compound 1 was purified by column chromatography (SiO2, hexane/acetone 8:1)
9. customyielding 8.74 g (62.81%)

ORD record

ord-83b7d456cab04b48b3d83f53d24adae2

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08877163B2