1,4-Dioxane → 1-Amino-1H-pyrrole-2-carbonitrile hydrochloride

Temperature

0 °C

A 3L, 3-neck RB flask was fitted with a mechanical stirrer, nitrogen inlet, thermocouple/JKEM thermocontroller, addition funnel and ice water cooling bath. (2-Cyano-pyrrol-1-yl)-carbamic acid, tert-butyl ester (85 g, 0.41 mol) was added and dissolved with 1,4-dioxane (400 mL), then the stirred orange solution was cooled to 0° C. and HCl/dioxane (4N, 820 mL, 8 eq.) was slowly added from the addition funnel, maintaining an internal temperature below 5° C. After ˜30 minutes the solution became cloudy and stirring@ room temperature was continued for 5 hours; the reaction was monitored for completion by TLC (silica gel, GHLF, 1:3 EtOAc/hexane, UV; Note: the free base may be observed as a high-Rf spot and can be misinterpreted as incomplete reaction). The reaction mixture was diluted with diethyl ether (2 L) and the precipitated solids were collected by suction filtration and washed with ether (1 L). Drying (vacuum oven@50° C.) afforded the desired product as 50.5 g (85%) of a tan solid. 1H-NMR (CD3OD): 7.05 (dd, 1H, J=2.8, 1.9 Hz), 6.75 (dd, 1H, J=1.8, 4.2 Hz), 6.13 (dd, 1H, J=2.8, 4.4 Hz), 5.08 (s, 3H, NH3+); MS: GC/MS, m/z=108.2 [M+H].

1. additionthermocouple/JKEM thermocontroller, addition funnel and ice water cooling bath
2. temperaturemaintaining an internal temperature below 5° C
3. waitcloudy and stirring@ room temperature was continued for 5 hours
4. customcan be misinterpreted as incomplete reaction)
5. filtrationthe precipitated solids were collected by suction filtration
6. washwashed with ether (1 L)
7. customDrying (vacuum oven@50° C.)

ORD record

ord-1cc0a526980a4718bb58dacbdc11b2b3

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143393B2