Hydrochloric Acid → HCID 86684901, compound

Participants

Reaction Conditions

Reaction Steps

(1S,4S)-5-(1-Trifluoromethyl-cyclopropanecarbonyl)-2-oxa-5-aza-bicyclo[2.2.1]heptan-3-one (220 g, 883 mmol), 1-amino-cyclopropanecarbonitrile hydrochloride (140 g, 1.18 mol) and sodium 2-ethylhexanoate (97%, 230 g, 1.34 mol) were dissolved in water (1.32 L). The mixture was stirred for 20 h at 53° C. After cooling to room temperature, tetrahydrofuran (880 mL) was added and the mixture was acidified by addition of concentrated hydrochloric acid (37% m/m, 47 mL), followed by the addition of sodium chloride (440 g). After extraction with ethyl acetate (1×1.4 L, 3×550 mL), the combined organic extracts were dried over sodium sulfate and concentrated in vacuo. At a volume of ca. 1.5 L, the product started to crystallize upon addition of seed crystals. The volume of the suspension was further reduced to ca. 500 mL and cooled to 2° C. (ice bath). After stirring for 60 min, the crystals were filtered off, washed with ethyl acetate/heptane 1:1 (v/v, 600 mL) and heptane (300 mL), and dried in vacuo to provide the title compound as off-white crystals (255.0 g, 87%). 1H NMR (CDCl3, 400 MHz): δ 1.18-1.29 (m, 4H), 1.30-1.42 (m, 2H), 1.50-1.59 (m, 2H), 2.17-2.26 (m, 1H), 2.29 (d, J=14.5 Hz, 1H), 3.73 and 3.96 (ABX, JAB=11.8 Hz, JAX=4.3 Hz, JBX=0 Hz, each 1H), 4.43-4.53 (m, 2H), 4.81 (br d, J=8.3 Hz, 1H), 7.73 (s, 1H).

Provenance & Evidence