Acetaldehyde → 1-chloroethyl (1R,3S,4S)-3-methoxy-4-(nitrooxy)cyclopentanecarboxylate

Temperature

0 °C

To a d-chloroform (60 mL) solution of (1R,3S,4S)-3-methoxy-4-(nitrooxy)cyclopentane carboxylic acid (4.59 g, 22.4 mmol) was added oxalyl chloride (2.40 mL, 27.4 mmol), followed by a few drops of N,N-dimethylformamide. After 60 minutes, 1H-NMR showed that the reaction was complete. To this reaction mixture was added zinc chloride (0.31 g, 2.27 mmol). The suspension was cooled to 0° C., and a d-chloroform solution (10 mL) of acetaldehyde (2.6 mL, 46.0 mmol) was slowly added to the reaction mixture over 5 minutes. The reaction was warmed up to room temperature and stirred for 17 hours. 1H-NMR confirmed that the starting acid chloride has been consumed and most of the material was converted to the desired product. The reaction mixture was concentrated in vacuo, and chromatography of the residue over silica gel, eluting with 2/98→20/80 ethyl acetate/hexanes, afforded the title compound as a colorless liquid. 1H NMR (500 MHz, CDCl3) δ 1.80 (d, J=5.9 Hz, 3H), 2.04-2.14 (m, 2H), 2.28-2.36 (m, 1H), 2.50-2.60 (m, 1H), 3.01 (quintet, J=8.3 Hz, 1H), 3.37 (s, 3H), 3.81-3.85 (m, 1H), 5.26-5.31 (m, 1H), 6.54 (q, J=5.8 Hz, 1H, D1), 6.54 (q, J=5.9 Hz, 1H, D2).

1. temperatureThe reaction was warmed up to room temperature
2. customhas been consumed and most of the material
3. concentrationThe reaction mixture was concentrated in vacuo, and chromatography of the residue over silica gel
4. washeluting with 2/98→20/80 ethyl acetate/hexanes

ORD record

ord-cb570c9997814bfdbd1c13ea0d40f3ce

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08293777B2