Hexane → 1-Amino-4-bromo-1H-pyrrole-2-carbonitrile hydrochloride

Temperature

0 °C

A 1 L, 3-neck flask was fitted with a mechanical stirrer, nitrogen inlet, thermocouple and 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 (4N, 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 at room temperature was continued for 7 hours. The reaction was monitored for completion by TLC (silica gel, 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 at 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); MS: GC/MS, m/z=[M+H].

1. customA 1 L, 3-neck flask was fitted with a mechanical stirrer, nitrogen inlet
2. temperaturethermocouple and 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 at 50° C.)

ORD record

ord-83579331ea0746c3b855d8189ce36bd3

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08431695B2