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

Temperature

0 °C

A 1 L, 3-neck RB flask was fitted with a mechanical stirrer, nitrogen inlet, thermocouple/JKEM thermocontroller, cooling bath and an addition funnel. tert-Butyl (4-bromo-2-cyano-1H-pyrrol-1-yl)carbamate (19 g, 66 mmol) was added and dissolved with 1,4-dioxane (50 mL), then the stirred orange solution was cooled to 0° C. and HCl/dioxane (4 N, 100 mL, 8 eq.) was slowly added from the addition funnel, maintaining an internal temperature around 25° C. After 2 hours the solution became cloudy and stirring @ room temperature was continued for 7 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 (150 mL) and the precipitated solids were collected by suction filtration and washed with ether (200 mL). Drying (vacuum oven @ 50° C.) afforded the desired product as 10.9 g (93%) of a white solid. 1H-NMR (DMSO): δ 7.24 (d, 1H, J=2 Hz), 6.93 (d, 1H, J=2 Hz), 6.2 (bs, 3H, J=2.8, 4.4 Hz).

1. customA 1 L, 3-neck RB flask was fitted with a mechanical stirrer, nitrogen inlet
2. temperaturethermocouple/JKEM thermocontroller, cooling bath and an addition funnel
3. temperaturemaintaining an internal temperature around 25° C
4. waitwas continued for 7 hours
5. customcan be misinterpreted as incomplete reaction)
6. filtrationthe precipitated solids were collected by suction filtration
7. washwashed with ether (200 mL)
8. customDrying (vacuum oven @ 50° C.)

ORD record

ord-09950f5f74894853a612796375497162

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08829185B2