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

Temperature

0 °C

A 3 L, 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): δ 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=1082 [M+H].

1. customA 3 L, 3-neck RB flask was fitted with a mechanical stirrer, nitrogen inlet
2. additionthermocouple/JKEM thermocontroller, addition funnel and ice water cooling bath
3. temperaturemaintaining an internal temperature below 5° C
4. waitwas continued for 5 hours
5. customcan be misinterpreted as incomplete reaction)
6. filtrationthe precipitated solids were collected by suction filtration
7. washwashed with ether (1 L)
8. customDrying (vacuum oven @ 50° C.)

ORD record

ord-064c1abb155f489aba0ab6572b7d55f7

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08431695B2